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ObjectiveThis paper aims to analyze the current status of outcome indicators in randomized controlled trials (RCT) of traditional Chinese medicine (TCM) for treating chronic atrophic gastritis (CAG), so as to provide references for constructing the core outcome set (COS) of TCM in the treatment of CAG. MethodChina National Knowledge Infrastructure (CNKI), Wanfang, VIP, SinoMed, PubMed, Embase, and Cochrane Library databases were searched for RCTs of TCM in the treatment of CAG in the last five years. The risk of bias of included studies was evaluated, and the selection status of outcome indicators was statistically analyzed. ResultA total of 150 RCTs were included, with a sample size of 44-398 cases. 164 outcome indicators were reported, with an application frequency of 1 229 times. The outcome indicators were classified into seven indicator domains according to functional attributes, followed by physical and chemical examination (69.41%), TCM syndrome (12.69%), symptoms and signs (11.15%), safety indicators (5.37%), quality of life (0.65%), long-term prognosis (0.65%), and economic evaluation (0.08%). According to the statistical analysis, there were problems in the selection of outcome indicators in RCTs of TCM for treating CAG, including various indicators, non-standard name reports, unclear primary and secondary indicators, random combination of subjective and objective indicators, neglected patient report outcome indicators, missing long-term prognosis and economic indicators, insufficient reporting of safety indicators, and inconsistent measurement tools and measurement time points. ConclusionIn the past five years, there have been many problems in the selection of outcome indicators in RCTs of TCM for treating CAG. It is necessary to actively promote the construction of the COS of TCM in the treatment of CAG and promote the high-quality development of clinical research of TCM.
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Purpose@#The microenvironment of pancreatic ductal adenocarcinoma (PDAC) with extensive desmoplastic stroma contributes to aggressive cancer behavior. Angiotensin system inhibitors (ASIs) reduce stromal fibrosis and are a promising therapeutic strategy. The purpose of this study was to examine how ASIs affected the oncological results of patients who had their PDAC removed. @*Materials and Methods@#A retrospective assessment was conducted on the clinicopathological and survival data of patients who received curative resection for PDAC at Severance Hospital between January 2012 and December 2019. @*Results@#A total of 410 participants (228 male and 182 female), with a median follow-up period of 12.8 months, were included in this study. Patients were divided into three groups, based on ASI use and history of hypertension: group 1, normotensive and never used ASI (n=210, 51.2%); group 2, ASI non-users with hypertension (n=50, 12.2%); and group 3, ASI users with hypertension (n=150, 36.6%). The three groups did not differ significantly in terms of age, sex, kind of operation, T and N stages, or adjuvant and neoadjuvant therapy. Moreover, there was no discernible difference in disease-free survival between those who used ASI and those who did not (p=0.636). The 5-year overall survival (OS) rates in groups 1, 2, and 3 were 52.6%, 32.3%, and 38.0%, respectively. However, the OS rate of ASI users was remarkably higher than that of non-users (p=0.016). @*Conclusion@#In patients with resected PDAC, ASI is linked to longer survival rates. Furthermore, for individuals with hypertension, ASI in conjunction with conventional chemotherapy may be an easy and successful treatment option.
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Background: Melasma is a chronic skin condition that adversely impacts quality of life. Although many therapeutic modalities are available there is no single best treatment for melasma. Oral tranexamic acid has been used for the treatment of this condition but its optimal dose is yet to be established. Objectives: We used network meta-analysis to determine the optimal dose of oral tranexamic acid for the treatment of melasma. Methods: We conducted a comprehensive search of all studies of oral tranexamic acid for the treatment of melasma up to September 2020 using PubMed, EMBASE and the Cochrane Library database. The quality of the studies was evaluated using the Jadad score and the Cochrane’s risk of bias assessment tool. Only high quality randomised controlled trials were selected. Some studies lacked standard deviation of changes from baseline and these were estimated using the correlation coefficient obtained from another similar study. Results: A total of 92 studies were identified of which 6 randomized controlled trials comprising 599 patients were included to form 3 pair-wise network comparisons. The mean age of the patients in these studies ranged from 30.3 to 46.5 years and the treatment duration ranged from 8 to 12 weeks. The Jadad scores ranged from 5 to 8. The optimal dose and duration of oral tranexamic acid was estimated to be 750 mg per day for 12 consecutive weeks. Limitations: Some confounding factors might not have been described in the original studies. Although clear rules were followed, the Melasma Area and Severity Index and the modified Melasma Area and Severity Index were scored by independent physicians and hence inter-observer bias could not be excluded. Conclusion: Oral tranexamic acid is a promising drug for the treatment of melasma. This is the first network meta-analysis to determine the optimal dose of this drug and to report the effects of different dosages. The optimal dose is 250 mg three times per day for 12 weeks, but 250 mg twice daily may be an acceptable option in poorly adherent patients. Our findings will allow physicians to balance drug effects and medication adherence. Personalized treatment plans are warranted.
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Prediction of the interactions between small molecules and their targets play important roles in various applications of drug development, such as lead discovery, drug repurposing and elucidation of potential drug side effects. Therefore, a variety of machine learning-based models have been developed to predict these interactions. In this study, a model called auxiliary multi-task graph isomorphism network with uncertainty weighting (AMGU) was developed to predict the inhibitory activities of small molecules against 204 different kinases based on the multi-task Graph Isomorphism Network (MT-GIN) with the auxiliary learning and uncertainty weighting strategy. The calculation results illustrate that the AMGU model outperformed the descriptor-based models and state-of-the-art graph neural networks (GNN) models on the internal test set. Furthermore, it also exhibited much better performance on two external test sets, suggesting that the AMGU model has enhanced generalizability due to its great transfer learning capacity. Then, a naïve model-agnostic interpretable method for GNN called edges masking was devised to explain the underlying predictive mechanisms, and the consistency of the interpretability results for 5 typical epidermal growth factor receptor (EGFR) inhibitors with their structure‒activity relationships could be observed. Finally, a free online web server called KIP was developed to predict the kinome-wide polypharmacology effects of small molecules (http://cadd.zju.edu.cn/kip).
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【Objective】 To conduct the laboratory quality assessment between 12 blood stations in Hebei province, analyze the results and explore the accuracy and comparability of testing, so as to improve the level of testing ability and quality management. 【Methods】 With reference to the external quality assessment rules of National Center for Clinical Laboratories and combined with the instructions of quality assessment samples, daily testing process of the laboratories were assessed. The quality indicators include blood cell count (WBC, RBC, Hb, HCT, MCV, MCH, MCHC and PLT), biochemical items (TP) and coagulation parameters (FIB and FⅧ). 【Results】 There are still problems in laboratories in terms of personnel operation, instrument maintenance and the impact of different reagent batches, especially in biochemical items and coagulation parameters. The pass rate of biochemical items was the lowest, only 72.75%, and that of blood cell count was the highest, reaching 98.75%. 【Conclusion】 With the progress of the project, the quality monitoring level of daily blood sampling tests in the quality control laboratory of each blood station has been improved. However, it is still necessary for each laboratory to improve the testing ability and quality management to a higher level in Hebei.
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Objective: To methodically assess the clinical effectiveness and safety of robot-assisted total rectal mesenteric resection (RTME), laparoscopic-assisted total rectal mesenteric resection (laTME), and transanal total rectal mesenteric resection (taTME). Methods: A computer search was conducted on PubMed, Embase, Cochrane Library, and Ovid databases to identify English-language reports published between January 2017 and January 2022 that compared the clinical efficacy of the three surgical procedures of RTME, laTME, and taTME. The quality of the studies was evaluated using the NOS and JADAD scales for retrospective cohort studies and randomized controlled trials, respectively. Direct meta-analysis and reticulated meta-analysis were performed using Review Manager software and R software, respectively. Results: Twenty-nine publications comprising 8,339 patients with rectal cancer were ultimately included. The direct meta-analysis indicated that the length of hospital stay was longer after RTME than after taTME, whereas according to the reticulated meta-analysis the length of hospital stay was shorter after taTME than after laTME (MD=-0.86, 95%CI: -1.70 to -0.096, P=0.036). Moreover, the incidence of anastomotic leak was lower after taTME than after RTME (OR=0.60, 95%CI: 0.39 to 0.91, P=0.018). The incidence of intestinal obstruction was also lower after taTME than after RTME (OR=0.55, 95%CI: 0.31 to 0.94, P=0.037). All of these differences were statistically significant (all P<0.05). There were no statistically significant differences between the three surgical procedures regarding the number of lymph nodes cleared, length of the inferior rectal margin, or rate of positive circumferential margins (all P>0.05). An inconsistency test using nodal analysis revealed no statistically significant differences between the results of direct and indirect comparisons of the six outcome indicators (all P>0.05). Furthermore, we detected no significant overall inconsistency between direct and indirect evidence. Conclusion: taTME has advantages over RTME and laTME, in terms of radical and surgical short-term outcomes in patients with rectal cancer.
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Humans , Robotics , Robotic Surgical Procedures/adverse effects , Network Meta-Analysis , Retrospective Studies , Postoperative Complications/etiology , Transanal Endoscopic Surgery/methods , Rectum/surgery , Rectal Neoplasms/pathology , Laparoscopy/methods , Treatment Outcomeالملخص
OBJECTIVE@#To improve the rat model of cervical spondylosis of vertebral artery type (CSA) induced by injecting sclerosing agent. To evaluate the efficacy of injecting sclerosing agent to induce CSA.@*METHODS@#Forty Health SPF SD rats(20 males and 20 females), were randomly divided into two groups:the model group (20) and the blank group (20). All the animals were followed up for 4 weeks for the observation of general situation, transcranial Doppler(TCD) detection of blood flow velocity, pulsatility index and resistive index of the vertebral artery, measurement of mental distress by open-field test.@*RESULTS@#One to two days after establish the animal model, rats in the model group appeared apathetic with decreased autonomic activities, trembling, squinting, increased eye excrement, etc., and no rats died during the experiment. The mean blood flow velocity of the model group was lower than that of the blank group (P<0.05), and the pulsatilit index and resistive index of the model group were higher than that of the blank group (P<0.05). The mental distress of the model group was significantly higher than that of the blank group.@*CONCLUSION@#The modified injection of sclerosing agent is a practical method to establish the rat model of CSA, with high success rate, high stability, low mortality and simple operation.
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Male , Animals , Female , Rats , Sclerotherapy , Sclerosing Solutions/therapeutic use , Rats, Sprague-Dawley , Spondylosis/therapy , Spine , Vertebral Arteryالملخص
Objective:To establish a new type of small intestinal organoids with injury-related regenerative capacity, and to simulate the process of intestinal injury, regeneration, and repair in vitro. Methods:The crypt structures of ileal mucosa from 6 to 8 weeks old, 18 to 24 g specific pathogen-free C57BL/6 mice were isolated. The ENR, ENR+ tumor necrosis factor-α(TNF-α) and 8C culture systems were designed to establish small intestinal organoids under conditions of intestinal homeostasis, inflammatory injury and injury-related regeneration, and the morphology of intestinal organoids were observed. The cell types and spatial arrangements of intestinal organoids, and the expression of genes clusterin( Clu), annexin A1( Anxa1), stem cell antigen-1( Sca1) and regenerating islet-derived protein 3-beta( Reg3 b) at protein levels were detected by immunofluorescence staining. The expression of genes Clu, Anxa1, Sca1 and Reg3 b at mRNA levels were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Independent sample- t test was used for statistical analysis. Results:In ENR and 8C culture system, both intestinal organoids contained intestinal stem cells, goblet cells, Paneth cells and intestinal endocrine cells, and the spatial arrangement of cells was similar to the intestinal epithelium. In the 8C culture system, the amplification capacity of the new small intestinal organoids was significantly enhanced, the growth rate was faster, and the structure was larger and more complex than those of small intestinal organoids in ENR and ENR+ TNF-α culture systems. The results of qRT-PCR showed that, the relative mRNA expression levels of novel small intestinal organoid regeneration genes Clu, Anxa1, and Sca1 in the 8C culture system were higher than those in the ENR and ENR+ TNF-α culture systems (0.68±0.31 vs.0.20±0.07 and 0.36±0.19, 0.48±0.13 vs. 0.07±0.02 and 0.18±0.11, 0.56±0.20 vs. 0.02±0.01 and 0.08±0.04), and the differences were statistically significant ( t=4.82 and 2.77, 8.62 and 4.89, and 8.58 and 7.50; all P<0.05). The results of immunofluorescence staining indicated that, the expression levels of novel small intestinal organoid regeneration genes Clu, Anxa1, Sca1 and Reg3 b at protein level in the 8C culture system were higher than those in the ENR and ENR+ TNF-α culture systems (31.62±1.69 vs. 9.73±2.39 and 15.11±2.16, 42.65±1.85 vs. 19.70±1.18 and 24.97±2.82, 63.80±2.73 vs. 37.10±1.59 and 43.27±2.53, 53.26±1.84 vs. 27.75±3.78 and 33.16±3.50), and the differences were statistically significant( t=12.95 and 10.41, 18.13 and 9.09, 14.63 and 9.56, and 10.51 and 8.80; all P<0.001). Conclusion:The small intestinal organoids established in the novel culture system have the characteristics of injury-related regeneration, and provide a novel in vitro model for studying the regeneration of epithelial tissues and organs.
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Objective To develop a traceable cancer hallmark ontology with terminology including gene mutation,cancer hallmark,and cell line for knowledge integration,standardization,correlation,and discovery.Methods The Ontology Development 101 and the current ontology development methods were employed to determine the content coverage,structural layers,reusable terms,and new terms of the cancer hallmark ontology.Taking colorectal cancer as a study case,we extracted the knowledge related with colorectal cancer hallmarks using text mining and text classification technology from PubMed,and then formalized the extracted knowledge into the cancer hallmark ontology.Moreover,we made use of existing cancer hallmark evidence in Catalogue of Somatic Mutations in Cancer and further semantic retrieval to discover new knowledge.Results The established cancer hallmark ontology comprised 9910 classes and 6138 instances,which realized the semantic representation of 2310 article abstracts about colorectal cancer and 26 pieces of evidence about genes and their cancer hallmarks.Compared with the Catalogue of Somatic Mutations in Cancer,new evidence for more genes associated with colorectal cancer hallmarks was found based on cancer hallmark ontology.Conclusion This study is of great significance to the research on the cancer pathogenesis at the molecular level,the revealing of specific roles of genes and mutations in the occurrence of cancer,and the rapid knowledge discovery of cancer hallmarks.
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Patients with acute heart failure (AHF) often experience dyspnea, and monitoring and quantifying their breathing patterns can provide reference information for disease and prognosis assessment. In this study, 39 AHF patients and 24 healthy subjects were included. Nighttime chest-abdominal respiratory signals were collected using wearable devices, and the differences in nocturnal breathing patterns between the two groups were quantitatively analyzed. Compared with the healthy group, the AHF group showed a higher mean breathing rate (BR_mean) [(21.03 ± 3.84) beat/min vs. (15.95 ± 3.08) beat/min, P < 0.001], and larger R_RSBI_cv [70.96% (54.34%-104.28)% vs. 58.48% (45.34%-65.95)%, P = 0.005], greater AB_ratio_cv [(22.52 ± 7.14)% vs. (17.10 ± 6.83)%, P = 0.004], and smaller SampEn (0.67 ± 0.37 vs. 1.01 ± 0.29, P < 0.001). Additionally, the mean inspiratory time (TI_mean) and expiration time (TE_mean) were shorter, TI_cv and TE_cv were greater. Furthermore, the LBI_cv was greater, while SD1 and SD2 on the Poincare plot were larger in the AHF group, all of which showed statistically significant differences. Logistic regression calibration revealed that the TI_mean reduction was a risk factor for AHF. The BR_ mean demonstrated the strongest ability to distinguish between the two groups, with an area under the curve (AUC) of 0.846. Parameters such as breathing period, amplitude, coordination, and nonlinear parameters effectively quantify abnormal breathing patterns in AHF patients. Specifically, the reduction in TI_mean serves as a risk factor for AHF, while the BR_mean distinguishes between the two groups. These findings have the potential to provide new information for the assessment of AHF patients.
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Humans , Heart Failure/diagnosis , Prognosis , Respiration , Wearable Electronic Devices , Acute Diseaseالملخص
Objective@#To detect WNT10A gene mutations in patients with oligodontia or anodontia (≥6 teeth missing) and analyze their dental phenotype. @*Methods@#Patients with oligodontia or anodontia were enrolled from the clinic for oral examination, genetic history collection and whole exon sequencing, and patients with WNT10A gene mutations were included. Sanger sequencing was utilized to validate the WNT10A gene variations in probands and family members compared with the normal sequence. The pathogenicity of WNT10A mutations was evaluated by functional prediction, conservation analysis and structure prediction of protein mutants. Implant rehabilitation was applied to restore the patients' oral function.@*Results@# Five WNT10A gene mutations were detected in six unrelated patients, and c.26G>A (p. Trp9X) and c.1036delT (p. Cys346fs) were novel mutations with pathogenic potential. The mean number of missing teeth was (15.33±8.64) per case. The most frequently missing permanent teeth were maxillary canines (100%), and the least frequently missing teeth were mandibular first molars (25%). Implant rehabilitation was applied in five patients, and patients were found to have ideal implant osseointegration and functional restoration.@*Conclusion @# This study identified novel WNT10A gene pathogenic variants, enriching the WNT10A gene spectrum and providing new evidence for genetic diagnosis and prenatal consultation. Implant rehabilitation was also proven to be a treatment option for these patients.
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Objective To establish the model of goat intervertebral disc degeneration (IDD) induced by controllable axial compressive stress and evaluate its imaging and pathological characteristics. Methods Twenty goats were randomly divided into 4 groups (control group, 4-week pressure group, 8-week pressure group, 12-week pressure group, n=5, 40 N pressure). Disc height index (DHI) was used to evaluate the change of intervertebral disc height by X-ray, Pfirrmann classification method was used to observe the degree of intervertebral disc degeneration by magnetic resonance imaging (MRI), and histopathological observation and evaluation for intervertebral disc were conducted by HE staining and immunohistochemistry. Results DHI in control group showed no significant changes with the extension of pressure time, while DHI in the experimental group gradually decreased. There was no significant change in Pfirrmann classification in control group. In experimental group, with the extension of time, the higher the degeneration aggravated with the Pfirrmann classification increasing. In experimental group, HE staining showed that the disc nucleus pulposus decreased in volume and nucleus pulposus cells, which were gradually replaced by fibrous tissues. Immunohistochemical staining showed that type I collagen in the nucleus pulposus gradually increased, type Ⅱ collagen gradually decreased, and intervertebral disc degeneration occurred. Conclusions A certain axial compressive stress can lead to degeneration of goat lumbar intervertebral disc, and the degree of degeneration is gradually increased with the extension of time.
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Background/Aims@#MicroRNAs (miRNAs) play critical regulatory roles in the pathogenesis of pulmonary fibrosis. The aim of this study was to explore whether miRNA antagomirs could serve as potential therapeutic agents in interstitial lung diseases. @*Methods@#A mouse model of pulmonary fibrosis was established by intratracheal injection of bleomycin (BLM). Using microarray analysis, up-regulated miRNAs were identified during the development of pulmonary fibrosis. miR-155 was chosen as the candidate miRNA. Fifteen mice were then randomized into the following three groups: BLM + antagomiR-155 group, treated with BLM plus intravenously injected with antagomiR-155; BLM group, treated with intratracheal BLM plus phosphate-buffered saline (PBS); and a control group, treated with PBS only. Lung tissues were collected for histopathological analysis, hydroxyproline measurement, and Western blotting. Enzyme-linked immunosorbent assays were used for the measurement of cytokines associated with pulmonary fibrosis. @*Results@#Histological changes and hydroxyproline levels induced by BLM were significantly inhibited by antagomiR-155. The levels of interleukin 4 (IL-4) and transforming growth factor-β (TGF-β) expression were increased after BLM treatment. However, miR-155 silencing decreased the expression of IL-4, TGF-β, and interferon-γ. TGF-β-activated kinase 1/mitogen-activated protein kinase kinase kinase 7 (MAP3K7)-binding protein 2 (TAB2) of the mitogen-activated protein kinase (MAPK) signaling pathway, was activated by BLM and inhibited by in vivo silencing of miR-155 via antagomiR-155. @*Conclusions@#In vivo treatment with antagomiR-155 alleviated the pathological changes induced by BLM and may be a promising therapeutic strategy for pulmonary fibrosis.
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A 57-year-old male patient was referred to our department with complaints of his right adrenal gland occupancy and hypertension about 6 months. When admitted to the hospital, the blood pressure was about 160/100 mmHg, and the heart rate was 110 beats/min. He was no obvious obesity, acne, abnormal mood, without weakness of limbs, acral numbness, palpitation and headache. He presented with type 2 diabetes for more than 3 years, with oral administration of metformin enteric coated tablets and subcutaneous injection of insulin glargine to control blood glucose, and satisfied with blood glucose control. Enhanced CT showed that: the right adrenal gland showed a kind of oval isodense, slightly hypodense shadow, the edge was clear, lobular change, the size was about 5.8 cm×5.4 cm, uneven density, there were nodular and strip calcification, round lipid containing area and strip low density area, and the CT value of solid part was about 34 HU. Enhanced scan showed heterogeneous nodular enhancement in the solid part of the right adrenal gland, nodular enhancement could be seen inside. The CT values of solid part in arterial phase, venous phase and delayed phase were 45 HU, 50 HU and 81 HU, respectively. Considering from the right adrenal gland, cortical cancer was more likely. No obvious abnormality was found in his endocrine examination. After adequate preoperative preparation, retroperitoneal laparoscopic adrenalectomy was performed under general anesthesia. During the operation, the 6 cm adrenal tumor was closely related to the inferior vena cava and liver, and after careful separation, the tumor was completely removed and normal adrenal tissue was preserved. The operation lasted 180 min and the blood loss was 100 mL, and the blood pressure was stable during and after the operation. There was no obvious complication. The results of pathological examinations were as follows: the size of the tumor was 7.5 cm×6.0 cm×3.5 cm, soft, with intact capsule and grayish-red cystic in section. Pathological diagnosis: (right adrenal gland) cavernous hemangioma, secondary intravascular thrombosis, old hemorrhagic infarction with calcification and ossification. After 6 months of observation, no obvious complications and tumor recurrence were found. In summary, cavernous hemangioma of adrenal gland is a rare histopathological change. Its essence is a malformed vascular mass. Blood retention is the cause of thrombosis and calcification in malformed vessels. The imaging findings were inhomogeneous enhancement of soft tissue masses, and the adrenal function examination showed no obvious abnormalities. Retroperitoneal laparoscopic surgery is feasible after adequate preoperative preparation. It is difficult to diagnose the disease preoperatively and needs to be confirmed by postoperative pathology.
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Humans , Male , Middle Aged , Adrenal Gland Neoplasms/surgery , Adrenalectomy , Diabetes Mellitus, Type 2 , Hemangioma, Cavernous/surgery , Laparoscopy , Neoplasm Recurrence, Localالملخص
ABSTRACT: Based on the data of "employment and food demand of urban migrant workers", this paper empirically analyzed the impact of urban pension insurance on the nutritional intake structure of migrant workers. The results showed that participating in urban pension insurance can change the nutritional intake structure of migrant workers. Additionally, fat and protein replace carbohydrate as the main nutrition sources for migrant workers. After controlling the income and labor intensity of migrant workers and other factors, urban pension insurance has a positive effect on the intake of fat and protein of migrant workers for they increase by 13.5% and 8.8% respectively. There is no significant effect on the intake of carbohydrates of migrant workers. The calorie intake of migrant workers increases by 6.8% accounting for the change of nutritional intake structure. Endogenous and robustness tests showed that the above conclusions are robust. Heterogeneity analysis showed that there is no significant difference in the effect of urban pension insurance on calorie intake of migrant workers in different income levels and age groups.
RESUMO: Este artigo usa os dados da pesquisa de "Emprego e demanda alimentar dos trabalhadores migrantes urbanos" para analisar empiricamente o impacto do seguro patrimonial urbano na estrutura de ingestão nutricional dos trabalhadores migrantes. O estudo constatou que: o seguro-pensão urbano mudou a estrutura de ingestão nutricional dos trabalhadores migrantes. Gordura e proteína substituíram os carboidratos e se tornaram a principal fonte de nutrição dos trabalhadores migrantes. Depois de controlar fatores como a renda e a intensidade do trabalho dos trabalhadores migrantes, o seguro de pensão urbana aumentou significativamente a ingestão de gordura e proteína dos trabalhadores migrantes em 13,5% e 8,8%, respectivamente, enquanto a ingestão de carboidratos dos trabalhadores migrantes não foi afetada. Significativamente afetado. A transformação da estrutura de ingestão nutricional dos trabalhadores migrantes aumentou sua ingestão calórica em 6,8%. Os testes de endogenia e robustez mostram que as conclusões acima são robustas. A análise de heterogeneidade mostra que não há diferença significativa no efeito do seguro previdenciário urbano sobre o aumento da ingestão de calorias para trabalhadores migrantes de diferentes níveis de renda e diferentes grupos etários.
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Many human genetic diseases, including Hutchinson-Gilford progeria syndrome (HGPS), are caused by single point mutations. HGPS is a rare disorder that causes premature aging and is usually caused by a de novo point mutation in the LMNA gene. Base editors (BEs) composed of a cytidine deaminase fused to CRISPR/Cas9 nickase are highly efficient at inducing C to T base conversions in a programmable manner and can be used to generate animal disease models with single amino-acid substitutions. Here, we generated the first HGPS monkey model by delivering a BE mRNA and guide RNA (gRNA) targeting the LMNA gene via microinjection into monkey zygotes. Five out of six newborn monkeys carried the mutation specifically at the target site. HGPS monkeys expressed the toxic form of lamin A, progerin, and recapitulated the typical HGPS phenotypes including growth retardation, bone alterations, and vascular abnormalities. Thus, this monkey model genetically and clinically mimics HGPS in humans, demonstrating that the BE system can efficiently and accurately generate patient-specific disease models in non-human primates.
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Animals , Female , Humans , Disease Models, Animal , Gene Editing , Lamin Type A/metabolism , Macaca fascicularis , Progeria/pathologyالملخص
Objective To analyze the epidemic trend of hepatitis B virus (HBV) in 18 minority nationalities in Yunnan Province from 2009 to 2018, so as to explore the ethnic differences in the incidence of HBV in Yunnan Province. Methods Based on the reported incidence data of hepatitis B in China's disease prevention and control information system from 2009 to 2018, descriptive epidemiology method was used to describe and analyze the incidence of hepatitis B in different ethnic groups, and K-means clustering method was used to explore and analyze the annual average incidence of hepatitis B in different ethnic groups. Results From 2009 to 2018, the average incidence of hepatitis B in Yunnan Province was 44.26/100 000, which was much lower than the overall level of China every year; the average incidence of hepatitis B in ethnic groups was 41.27/100 000, slightly lower than the overall level of Yunnan every year. The prevalence of hepatitis B was different in different ethnic groups. The average incidence of Wa was significantly higher than others (95.26/100 000), and Jingpo was the lowest (22.51/100 000). According to the incidence of hepatitis B, different ethnic groups were divided into three categories: high incidence ethnic group, middle incidence ethnic group and low incidence ethnic group. Conclusion There are ethnic differences in the incidence of hepatitis B in Yunnan Province. The incidence of hepatitis B in some ethnic groups is higher than that in the whole country all the year round, which is the key population in the prevention and control of hepatitis B.
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The recent pneumonia outbreak caused by a novel coronavirus (SARS-CoV-2) is posing a great threat to global public health. Therefore, rapid and accurate identification of pathogenic viruses plays a vital role in selecting appropriate treatments, saving people's lives and preventing epidemics. It is important to establish a quick standard diagnostic test for the detection of the infectious disease (COVID-19) to prevent subsequent secondary spread. Polymerase chain reaction (PCR) is regarded as a gold standard test for the molecular diagnosis of viral and bacterial infections with high sensitivity and specificity. Isothermal nucleic acid amplification is considered to be a highly promising candidate method due to its fundamental advantage in quick procedure time at constant temperature without thermocycler opera-tion. A variety of improved or new approaches also have been developed. This review summarizes the currently available detection methods for coronavirus nucleic acid. It is anticipated that this will assist researchers and clinicians in developing better techniques for timely and effective detection of coro-navirus infection.
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Objective: To study the secondary metabolites of marine-derived Aspergillus fumigatus MDCW-15. Methods: The secondary metabolites were isolated and purified by column chromatography over silica gel. And their structures were identified by the spectroscopic analysis of NMR and MS. The antifungal bioactivities were assayed by paper diffusion. Results: A new fumagillin compound 1 and a known compound 2 were isolated from the fermentation broth of marine-derived Aspergillus fumigatus MDCW-15. The antifungal bioactivities were assayed by paper diffusion. Compounds 1 and 2 showed antifungal activity against Candida albicans with an equal MIC value of 32.0 μg/mL. Conclusion: Compound 1 is a new compound named 2'-cis- fumagiringillin. Compounds 1 and 2 exhibit antifungal activities.
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BACKGROUND@#Carbapenemase-producing Klebsiella pneumoniae (CP-Kp) poses distinct clinical challenges due to extensively drug resistant (XDR) phenotype, and sequence type (ST) 11 is the most dominant blaKPC-2-bearing CP-Kp clone in China. The purpose of this current retrospective study was to explore the genetic factors associated with the success of XDR CP-Kp ST11 strains circulated in the intensive care unit (ICU) of a Chinese tertiary hospital.@*METHODS@#Six ST11 XDR CP-Kp strains were identified between May and December 2014 and validated by minimum inhibitory concentration examination, polymerase chain reaction, and pyrosequencing. The six ST11 XDR CP-Kp, as well as three multi-drug resistant (MDR) and four susceptible strains, were sequenced using single-molecule real-time method. Comprehensively structural and functional analysis based on comparative genomics was performed to identify genomic characteristics of the XDR ST11 CP-Kp strains.@*RESULTS@#We found that ST11 XDR blaKPC-2-bearing CP-Kp strains isolated from inpatients spread in the ICU of the hospital. Functionally, genes associated with information storage and processing of the ST11 XDR CP-Kp strains were more abundant than those of MDR and susceptible strains, especially genes correlative with mobile genetic elements (MGEs) such as transposons and prophages. Structurally, eleven large-scale genetic regions taken for the unique genome in these ST11 XDR CP-Kp strains were identified as MGEs including transposons, integrons, prophages, genomic islands, and integrative and conjugative elements. Three of them were located on plasmids and eight on chromosomes; five of them were with antimicrobial resistance genes and eight with adaptation associated genes. Notably, a new blaKPC-2-bearing ΔΔTn1721-blaKPC-2 transposon, probably transposed and truncated from ΔTn1721-blaKPC-2 by IS903D and ISKpn8, was identified in all six ST11 XDR CP-Kp strains.@*CONCLUSION@#Our findings suggested that together with clonal spread, MGEs identified uniquely in the ST11 XDR CP-Kp strains might contribute to their formidable adaptability, which facilitated their widespread dissemination in hospital.