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Introduction: The relationship between different puncture points and perioperative complications and length of stay in hospital (LOS) in SCCAG patients has rarely been reported. Aim: To compare the curative effect and safety of the transradial artery approach and the transfemoral artery approach in combined heart-brain angiography. Material and methods: 120 patients who received combined cardio-cerebral angiography in our hospital were selected and divided into a transradial artery approach group (TRA) and a transfemoral artery approach group (TFA) according to a random number table. The postoperative efficacy and safety of the 2 groups were compared. Results: There was no statistically significant difference in puncture time and operation time between the 2 groups (p > 0.05). Postoperative bed rest time, hospitalization time, and X-ray exposure time in the TRA group were shorter than those in the TFA group, and the difference was statistically significant (p < 0.05). Before operation and 3 days after operation, there was no significant difference in left ventricle ejection fraction between the 2 groups (p > 0. 05). The overall incidence of complications in the TFA group was higher than that in the TRA group. The incidence between haematoma and pseudoaneurysm in the TFA group was higher, and the difference was statistically significant (p < 0.05). Conclusions: For simultaneous heart-brain angiography, interventional therapy via radial artery and femoral artery has good curative effect and can improve cardiac function. However, interventional therapy through the radial artery can shorten the postoperative bed rest time and hospitalization time, and reduce the incidence of complications.
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Fragile X syndrome is the leading genetic cause of intellectual disability and autism spectrum disorders. Female premutation carriers exhibit no obvious symptoms during reproductive age, but the premutation allele can expand to full mutation when transmitted to the fetus. Given the relatively low prevalence but large population, the distinct health care system, the middle-income economic status, and low awareness among public and medical professionals, the optimal genetic screening strategy remains unknown. We conducted a pilot study of Fragile X carrier screening in China, involving 22,245 pregnant women and women with childbearing intentions, divided into control and pilot groups. The prevalence of Fragile X carriers in the control group was 1 of 850, similar to East Asian populations. Strikingly, the prevalence of Fragile X carriers in the pilot group was 1 of 356, which can be attributed to extensive medical training, participant education, and rigorous genetic counseling and testing protocols. Cost-effectiveness analyses of four strategies-no screening, population-based screening, targeted screening, and our pilot screening-indicated that our pilot screening was the most cost-effective option. A follow-up survey revealed that 55% of respondents reported undergoing screening because of their family history. We have successfully established a standardized system, addressing the challenges of low prevalence, limited awareness, and genetic testing complexities. Our study provides practical recommendations for implementing Fragile X carrier screening in China.
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Dehydration of alcohols is one of the most fundamental transformations in the organic chemistry class and one of the most widely used methods for producing alkenes in synthetic research. Numerous methods and reagents have been developed to control the regio- and stereoselectivity as well as the dehydration efficiency of normal alcohols. Despite these achievements, regio- and stereoselective and predictable dehydration of allylic alcohol has seldom been reported, except for limited substrates with a native preferred elimination position, as a result of the challenges that many potential dienes could be formed via 1,2- or 1,4-syn- or anti-elimination. Here, we report a tBuOK/potassium 2,2-difluoroacetate-mediated 1,4-syn-dehydration of allylic alcohol for the synthesis of regio- and stereodefined conjugated dienes via an in situ generated directing group strategy. This reaction exhibits a broad substrate scope and good functional group compatibility for primary-tertiary alcohols. The simple and scalable (up to 0.6 mol) procedure with readily available and inexpensive reagents makes it a practical method for conjugated diene synthesis. Mechanistic studies reveal that an acetate with tert-butoxide and allyloxide acetal moiety is formed as an intermediate, in which the acetate and the acetal act as the directing group for the base-promoted elimination. An unusual H2 evolution is also involved in the reaction.
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BACKGROUND: Knee osteoarthritis (KOA) is a chronic musculoskeletal disorder characterized by pain and functional impairment. Blood flow restriction (BFR) with low-load resistance training (LLRT) demonstrates a similar improvement in clinical outcomes to high-load resistance training (HLRT) in treating KOA. It has not been established whether intermittent blood flow restriction (iBFR) with LLRT can lead to clinical outcomes that are comparable to those produced by continuous blood flow restriction (cBFR) with LLRT and HLRT. The aim of the proposed study is to evaluate the efficacy of iBFR with LLRT on pain, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), muscle strength, muscle mass, physical function, perceptions of discomfort and effort, and adherence in KOA patients. METHODS: This is a three-arm, non-inferiority, randomized controlled trial utilizing blinded assessors. Two hundred thirteen participants will be randomly allocated to one of the following three groups: iBFR group-receiving 4 months of LLRT with iBFR, twice weekly (n = 71); cBFR group-receiving 4 months of LLRT with cBFR, twice weekly (n = 71); or HLRT group-receiving 4 months of HLRT without BFR, twice weekly (n = 71). The primary outcome is pain. The secondary outcomes include the WOMAC, muscle strength, muscle mass, physical function, perceptions of discomfort and effort, and adherence. Pain and WOMAC will be measured at the baseline and 4 and 12 months after randomizations. Muscle strength, muscle mass, and physical function will be measured at the baseline and 4 months after randomizations. The perceptions of discomfort and effort will be measured during the first and final sessions. DISCUSSION: BFR with LLRT has a similar improvement in clinical outcomes as HLRT. However, cBFR may cause elevated ratings of perceived exertion and local discomfort, compromising patient tolerability and treatment adherence. If iBFR with LLRT could produce improvement in clinical outcomes analogous to those of HLRT and iBFR with LLRT, it could be considered an alternative approach for treating patients with KOA. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2300072820. Registered on June 26, 2023.
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Terapia de Restrição de Fluxo Sanguíneo , Força Muscular , Osteoartrite do Joelho , Treinamento Resistido , Humanos , Treinamento Resistido/métodos , Osteoartrite do Joelho/fisiopatologia , Osteoartrite do Joelho/terapia , Idoso , Resultado do Tratamento , Terapia de Restrição de Fluxo Sanguíneo/métodos , Feminino , Masculino , Pessoa de Meia-Idade , Estudos de Equivalência como Asunto , Medição da Dor , Fluxo Sanguíneo Regional , Ensaios Clínicos Controlados Aleatórios como Assunto , Recuperação de Função Fisiológica , Fatores de Tempo , Articulação do Joelho/fisiopatologiaRESUMO
Long-chain esters (LCEs) are known to affect aroma perception, but the mechanism of their effects remains unclear. In this study, ethyl palmitate (EP), an important LCE in Osmanthus fragrans flower absolute (OFFA), was selected as a target to identify its role and mechanism. The release characteristics of 10 aroma compounds from OFFA with and without EP were obtained by headspace gas chromatography mass spectrometry (HS-GC/MS) and olfactometry evaluation, respectively. The results show that EP changes the release behaviors of volatile compounds in solution, increases their olfactory detection thresholds (ODTs), and reduces the equilibrium headspace concentrations. According to Whitman's two-film model, EP was found to change the partition coefficients and mass transfer coefficients of the compounds between the liquid and gas phases. This indicates that EP plays an important role in the scent formation of a flavor product and that it is very valuable for the style design of the flavor product.
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BACKGROUND: Recurrent pregnancy loss (RPL) is a common pregnancy complication that brings great pain to pregnant women and their families. Genetic factors are an important cause reason of RPL. However, clinical research on monogenic diseases with recurrent miscarriage is insufficient. CASE PRESENTATION: Here we reported a Chinese family with RPL and genetic analysis of the abortion and parents. A paternally inherited heterozygous missense variant c.1415T > G (p.V472G) and a maternally inherited heterozygous nonsense variant c.2314del (p.M772*) in TMEM67 gene were identified by trio-exome sequencing. c.2314del (p.M772*) generated a premature stop codon and truncated protein, was classified as "pathogenic". c.1415T > G (p.V472G) located in extra-cellular region, was classified as "likely pathogenic". Biallelic variants in TMEM67 gene cause lethal Meckel syndrome 3, consistent with the proband's prenatal phenotype. CONCLUSION: The current study of the Chinese family expands the pathogenic variant spectrum of TMEM67 and emphasizes the necessity of exome sequencing in RPL condition.
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Aborto Habitual , Proteínas de Membrana , Linhagem , Humanos , Feminino , Proteínas de Membrana/genética , Aborto Habitual/genética , Gravidez , Adulto , Povo Asiático/genética , Masculino , Sequenciamento do Exoma , China , População do Leste AsiáticoRESUMO
α-thalassemia is a type of microcytic hypochromic anemia caused by variants of alpha-globin gene, and is one of the most common monogenic disorders in southern China. The population screening model based on hematologic phenotype has achieved great results in areas with high incidence of thalassemia. However, with the continuous decline of the cost of genetic testing and implementation of screening programs for thalassemia gene carriers, more variants in the alpha-globin gene have been discovered, which also brings great challenges to clinical genetic counseling. From the perspective of alpha-globin genetic analysis, this consensus has discussed the contents of pre- and post-test genetic counseling, with an aim to provide standardized guidance for clinicians.
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Aconselhamento Genético , Talassemia alfa , Humanos , alfa-Globinas/genética , Talassemia alfa/genética , Talassemia alfa/diagnóstico , Consenso , Testes GenéticosRESUMO
Background: Carrier screening is the most effective method to block the occurrence of thalassemia. However, due to differences in race and genotype, MCV, MCH, HbA2 and other indicators are far from each other. The purpose of this study is to evaluate the common screening indicators of a, b and ab-compound thalassemia carriers in Hunan Province, and try to use the relevant formulas in the existing literature to predict and distinguish different types of thalassemia carriers. Methods: Receiver operating characteristic curve (ROC curve) combined with Youden index was utilized to analyze results of blood routine examination, hemoglobin electrophoresis, and literature-related formulas for 1111 a-thalassemia carriers, 464 b-thalassemia carriers and 24 ab-thalassemia carriers.
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AIMS: The study aimed to evaluate the effects of dietary folic acid (FA) on the production performance of laying hens, egg quality, and the nutritional differences between eggs fortified with FA and ordinary eggs. METHODS: A total of 288 26-week-old Hy-Line Brown laying hens (initial body weights 1.65 ± 0.10 kg) with a similar weight and genetic background were used. A completely randomized design divided the birds into a control group and three treatment groups. Each group consisted of six replicates, with twelve chickens per replicate. Initially, all birds were fed a basal diet for 1 week. Subsequently, they were fed a basal diet supplemented with 0, 5, 10, or 15 mg/kg FA in a premix for a duration of 6 weeks. RESULTS: Supplementation of FA could significantly (p < 0.05) enhance the FA content in egg yolks, particularly when 10 mg/kg was used, as it had the most effective enrichment effect. Compared to the control group, the Glu content in the 10 and 15 mg/kg FA groups showed a significant (p < 0.05) decrease. Additionally, the contents of Asp, Ile, Tyr, Phe, Cys, and Met in the 15 mg/kg FA group were significantly (p < 0.05) lower compared to the other groups. Adding FA did not have significant effects on the levels of vitamin A and vitamin E in egg yolk, but the vitamin D content in the 5 and 10 mg/kg FA groups showed a significant (p < 0.05) increase. Furthermore, the addition of FA did not have a significant effect on the levels of Cu, Fe, Mn, Se, and Zn in egg yolk. The dietary FA did not have a significant effect on the total saturated fatty acids (SFA) and polyunsaturated fatty acid (PUFA) content in egg yolk. However, the total monounsaturated fatty acid (MUFA) content in the 5 and 10 mg/kg groups significantly (p < 0.05) increased. These changes in nutritional content might be attributed to the increased very low-density lipoprotein (VLDL) protein content. The significant decrease in solute carrier family 1 Member 1 (SLC1A1), solute carrier family 1 Member 2 (SLC1A2), and solute carrier family 1 Member 3 (SLC1A3) gene expression compared to the control group appeared to be the reason for the decrease in amino acid content in egg yolk within the dietary FA group. CONCLUSION: The findings suggest that the appropriate addition of FA can enhance the levels of MUFA and vitamin D in egg yolks, thereby improving their nutritional value. Excessive intake of FA can decrease the effectiveness of enriching FA in egg yolk and impact the enrichment of certain amino acids. The yolk of eggs produced by adding 10 mg/kg of FA to the feed contains the optimal amount of nutrients. This study informs consumers purchasing FA-fortified eggs.
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A 58-year-old male patient was admitted to Peking University First Hospital (Beijing, China) due to recurrent hematuria, proteinuria and kidney dysfunction. The patient was positive for proteinase-3 (PR3)-antineutrophil cytoplasmic antibody (ANCA). Pathology of the kidney showed focal proliferative necrotizing glomerulonephritis with crescent formation and immune complex-mediated glomerulonephritis. The patient was diagnosed with PR3-ANCA-associated vasculitis (AAV), received intensive immunosuppressive therapy and experienced two relapses within 1 year. After admission, aortic valve vegetation was observed via echocardiography. The patient subsequently received antibiotic treatment and valve replacement, and achieved complete remission of kidney and cardiac function. The present case emphasized the importance of identifying secondary reasons for ANCA formation, especially infective endocarditis in patients with PR3-AAV.
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Development of combined mass spectrometry ionization sources has enabled expansion of the application and scope of mass spectrometry. A novel hybrid ionization system combining vacuum ultraviolet (VUV) and atmospheric pressure chemical ionization (APCI) was constructed. Gaseous samples were self-aspirated into an ionization zone through a capillary by negative pressure, generated by high-speed airflow based on the Venturi effect. Compared with APCI mode alone, the signal-to-noise ratio (S/N) in APCI/VUV mode was increased by about 276-times. To increase the ionization efficiency further, correlated experimental conditions were optimized. Four types of volatile organic compounds (VOCs) were tested to evaluate the performance of the APCI/VUV ion source. Excellent linearity and limit of detection were achieved for compounds in mixed solutions. Quantitative analyses of four VOCs (toluene, cyclohexanone, styrene and ethylbenzene) using APCI/VUV-MS were done, and the relative standard deviations (RSDs) were 1.57%, 6.30%, 4.49% and 8.21%, respectively, indicating that the APCI/VUV ionization source had excellent reproducibility. Our results demonstrated that the developed method was promising for analyzing VOCs as well as being rapid, simple, and easy to operate.
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As a common disease, canker seriously affects the yield and quality of fragrant pear due to the lack of effective control measures. Some fungi have been reported to harbor rich reservoirs of viral resources, and some mycoviruses can be used as biocontrol agents against plant diseases. In this study, 199 isolates were obtained from diseased branches of fragrant pear in the main production areas of Xinjiang. Among them, 134 belonged to Valsa spp., identified using morphological and molecular biological techniques, in which V. mali was the dominant species. The mycoviruses in Valsa spp. were further identified using metatranscriptomic sequencing and RT-PCR. The results revealed that a total of seven mycoviruses were identified, belonging to Botourmiaviridae, Endornaviridae, Fusariviridae, Hypoviridae, Mitoviridae, and Narnaviridae, among which Phomopsis longicolla hypovirus (PlHV) was dominant in all the sample collection regions. The Cryphonectria hypovirus 3-XJ1 (CHV3-XJ1), Botourmiaviridae sp.-XJ1 (BVsp-XJ1), and Fusariviridae sp.-XJ1 (Fvsp-XJ1) were new mycoviruses discovered within the Valsa spp. More importantly, compared with those in the virus-free Valsa spp. strain, the growth rate and virulence of the VN-5 strain co-infected with PlHV and CHV3-XJ1 were reduced by 59% and 75%, respectively, and the growth rate and virulence of the VN-34 strain infected with PlHV were reduced by 42% and 55%, respectively. On the other hand, the horizontal transmission efficiency of PlHV decreased when PlHV was co-infected with CHV3-XJ1, indicating that PlHV and CHV3-XJ1 were antagonistic. In summary, the mycoviruses in Valsa spp. were identified in Xinjiang for the first time, and three of them were newly discovered mycoviruses, with two strains yielding good results. These results will offer potential biocontrol resources for managing pear canker disease and provide a theoretical basis for the control of fruit tree Valsa canker disease.
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Ascomicetos , Micovírus , Phomopsis , Pyrus , Vírus de RNA , Micovírus/genética , Vírus de RNA/genética , Doenças das Plantas/microbiologiaRESUMO
Background: Pleomorphic adenoma (PA), often with the benign-like imaging appearances similar to Warthin tumor (WT), however, is a potentially malignant tumor with a high recurrence rate. It is worse that pathological fine-needle aspiration cytology (FNAC) is difficult to distinguish PA and WT for inexperienced pathologists. This study employed deep learning (DL) technology, which effectively utilized ultrasound images, to provide a reliable approach for discriminating PA from WT. Methods: 488 surgically confirmed patients, including 266 with PA and 222 with WT, were enrolled in this study. Two experienced ultrasound physicians independently evaluated all images to differentiate between PA and WT. The diagnostic performance of preoperative FNAC was also evaluated. During the DL study, all ultrasound images were randomly divided into training (70%), validation (20%), and test (10%) sets. Furthermore, ultrasound images that could not be diagnosed by FNAC were also randomly allocated to training (60%), validation (20%), and test (20%) sets. Five DL models were developed to classify ultrasound images as PA or WT. The robustness of these models was assessed using five-fold cross-validation. The Gradient-weighted Class Activation Mapping (Grad-CAM) technique was employed to visualize the region of interest in the DL models. Results: In Grad-CAM analysis, the DL models accurately identified the mass as the region of interest. The area under the receiver operating characteristic curve (AUROC) of the two ultrasound physicians were 0.351 and 0.598, and FNAC achieved an AUROC of only 0.721. Meanwhile, for DL models, the AUROC value for discriminating between PA and WT in the test set was from 0.828 to 0.908. ResNet50 demonstrated the optimal performance with an AUROC of 0.908, an accuracy of 0.833, a sensitivity of 0.736, and a specificity of 0.904. In the test set of cases that FNAC failed to provide a diagnosis, DenseNet121 demonstrated the optimal performance with an AUROC of 0.897, an accuracy of 0.806, a sensitivity of 0.789, and a specificity of 0.824. Conclusion: For the discrimination of PA and WT, DL models are superior to ultrasound and FNAC, thereby facilitating surgeons in making informed decisions regarding the most appropriate surgical approach.
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BACKGROUND: As a holoparasitic weed, broomrape has seriously threatened the production of economically important crops, such as melon, watermelon, processed tomato, and sunflower, in Xinjiang in recent years. However, the distribution and genetic diversity of broomrape populations in Xinjiang are not clear at present, which hinders their prevention and control. The purpose of this study was to identify the main species and the genetic differentiation structure of the broomrape population in Xinjiang. METHODS AND RESULTS: In the present study, 93 samples from different geographic regions of Xinjiang were collected to identify the species based on ITS and plastid rps2 regions, and the samples were also used to analyze the genetic diversity based on ISSR markers. The results showed that broomrape is not monophyletic in Xinjiang and consists of two major clades (Orobanche cf. aegyptiaca and O. cernua) and three subclades (O. cf. aegyptiaca var. tch, O. cf. aegyptiaca var. klz, and O. cernua.var. alt) based on phylogenetic analysis. Furthermore, the results of the genetic diversity analysis indicated that the average polymorphic information content and marker index were high values of 0.58 and 7.38, respectively, showing the efficiency of the ISSR markers in detecting polymorphism among the broomrape population studied. Additionally, the 11 selected primers produced 154 repeatable polymorphic bands, of which 150 were polymorphic. The genetic diversity of the samples was 37.19% within populations and 62.81% among the populations, indicating that the main genetic differentiation occurred among the populations. There was less gene exchange between populations, with a gene flow index (Nm) of 0.2961 (< 1). The UPGMA dendrogram indicated that most populations with similar geographical conditions and hosts were clustered first, and then all samples were separated into two major groups and seven subclusters. CONCLUSION: The broomrapes are mainly O. cf. aegyptiaca and O. cernua in Xinjiang, which were separated into two major groups and seven subclusters based on ISSR markers. Our results provide a theoretical basis for breeding broomrape-resistant varieties.
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Orobanche , Variação Genética/genética , Filogenia , Melhoramento Vegetal , ChinaRESUMO
INTRODUCTION: Renal fibrosis (RF), being the most important pathological change in the progression of CKD, is currently assessed by the evaluation of a biopsy. This present study aimed to apply a novel functional MRI (fMRI) protocol named amide proton transfer (APT) weighting to evaluate RF noninvasively. METHODS: Male Sprague-Dawley (SD) rats were initially subjected to bilateral kidney ischemia/reperfusion injury (IRI), unilateral ureteral obstruction, and sham operation, respectively. All rats underwent APT mapping on the 7th and 14th days after operation. Besides, 26 patients underwent renal biopsy at the Nephrology Department of Shanghai Tongji Hospital between July 2022 and May 2023. Patients underwent APT and apparent diffusion coefficient (ADC) mappings within 1 week before biopsy. MRI results of both patients and rats were calculated by comparing with gold standard histology for fibrosis assessment. RESULTS: In animal models, the cortical APT (cAPT) and medullary APT (mAPT) values were positively correlated with the degree of RF. Compared to the sham group, IRI group showed significantly increased cAPT and mAPT values on the 7th and 14th days after surgery, but no group differences were found in ADC values. Similar results were found in human patients. Cortical/medullary APT values were significantly increased in patients with moderate-to-severe fibrosis than in patients with mild fibrosis. ROC curve analysis indicated that APT value displayed a better diagnostic value for RF. Furthermore, combination of cADC and cAPT improved fibrosis detection by imaging variables alone (p < 0.1). CONCLUSION: APT values had better diagnostic capability at early stage of RF compared to ADC values, and the addition of APT imaging to conventional ADC will significantly improve the diagnostic performance for predicting kidney fibrosis.
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Fibrose , Rim , Imageamento por Ressonância Magnética , Ratos Sprague-Dawley , Masculino , Animais , Fibrose/diagnóstico por imagem , Humanos , Ratos , Pessoa de Meia-Idade , Rim/diagnóstico por imagem , Rim/patologia , Imageamento por Ressonância Magnética/métodos , Traumatismo por Reperfusão/diagnóstico por imagem , Feminino , Adulto , Amidas , Prótons , Nefropatias/diagnóstico por imagem , Nefropatias/patologia , Nefropatias/diagnóstico , Idoso , Insuficiência Renal Crônica/diagnóstico por imagem , Insuficiência Renal Crônica/patologia , Obstrução Ureteral/diagnóstico por imagem , Modelos Animais de DoençasRESUMO
Fragile X syndrome is the most common inherited cause of intellectual disability. Considering China's low prevalence, distinct healthcare system, middle-income economic status, and unique culture, China cannot simply replicate the screening systems in European and American countries. In this study, we investigated the attitudes of 450 Chinese medical professionals who received fragile X training on fragile X carrier screening and genetic counseling. Before the training, 57.6% of the respondents were unfamiliar with FXS. After the training, 7.3% of participants are unable to fully master the knowledge. Furthermore, 71.8% believe that the absence of phenotypes during the reproductive age and the availability of simple and feasible testing methods are prerequisites for screening. The presence of the phenotype would still require screening. Regarding the target population, over 90% of the participants support fragile X carrier screening in high-risk pregnant women. As for influencing factors, they consider cost as the most influential factor in pregnant women's decision to undergo screening. The acceptable price range for screening is determined to be ï¿¥200-1000 ($30-150). In terms of the issues and challenges of screening, most medical professionals support the need for genetic counseling for intermediate alleles and 55-60 repeat premutation results. Additionally, some respondents believe that informing patients' family members of positive screening results is necessary. It is also recognized that positive results may lead to anxiety for patients. The findings of this study will provide valuable information for the establishment of fragile X carrier screening system, particularly for low-prevalence or middle-income countries.
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OBJECTIVE: To assess pelvic floor muscle (PFM) strength and influencing factors among healthy women at different life stages. DESIGN: Multicentre cross-sectional study. SETTING: Fourteen hospitals in China. POPULATION: A total of 5040 healthy women allocated to the following groups (with 1680 women per group): premenopausal nulliparous, premenopausal parous and postmenopausal. METHODS: The PFM strength was evaluated by vaginal manometry. Multivariate logistic regression was used to determine the influencing factors for low PFM strength. MAIN OUTCOME MEASURES: Maximum voluntary contraction pressure (MVCP). RESULTS: The median MVCP values were 36, 35 and 35 cmH2O in premenopausal nulliparous (aged 19-51 years), premenopausal parous (aged 22-61 years), and postmenopausal (aged 40-86 years) women, respectively. In the premenopausal nulliparous group, physical work (odds ratio, OR 2.05) was the risk factor for low PFM strength, which may be related to the chronic increased abdominal pressure caused by physical work. In the premenopausal parous group, the number of vaginal deliveries (OR 1.28) and diabetes (OR 2.70) were risk factors for low PFM strength, whereas sexual intercourse (<2 times per week vs. none, OR 0.55; ≥2 times per week vs. none, OR 0.56) and PFM exercise (OR 0.50) may have protective effects. In the postmenopausal group, the number of vaginal deliveries (OR 1.32) and family history of pelvic organ prolapse (POP) (OR 1.83) were risk factors for low PFM strength. CONCLUSIONS: Physical work, vaginal delivery, diabetes and a family history of POP are all risk factors for low PFM strength, whereas PFM exercises and sexual life can have a protective effect. The importance of these factors varies at different stages of a woman's life.
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Manometria , Força Muscular , Diafragma da Pelve , Pós-Menopausa , Pré-Menopausa , Vagina , Humanos , Feminino , Pessoa de Meia-Idade , Estudos Transversais , Diafragma da Pelve/fisiologia , Adulto , Manometria/métodos , Força Muscular/fisiologia , Idoso , Pós-Menopausa/fisiologia , Pré-Menopausa/fisiologia , Vagina/fisiologia , Fatores de Risco , Idoso de 80 Anos ou mais , Adulto Jovem , Paridade , China/epidemiologia , Contração Muscular/fisiologia , GravidezRESUMO
BACKGROUND AND OBJECTIVE: All-trans retinoic acid (ATRA), an effective differentiation inducer, has been applied clinically to treat acute promyelocytic leukemia (APL). Unfortunately, it is not as potent in other kinds of acute myeloid leukemia (AML). Ethacrynic acid (EA), a classical powerful diuretic, can increase reactive oxygen species (ROS) contents, which can assist ATRA in inducing differentiation in AML cells. Here, we investigated the effect of EA combined with ATRA (EA+RA) on some AML cells except APL. METHODS: Apoptosis and differentiation were determined by morphology, cell viability, Annexin-V assay and CD11c expression. Western blot analysis and the detection of ROS and mitochondrial transmembrane potentials (MMP) were used to investigate the mechanisms. RESULTS: AML cells exhibited differentiation and/or apoptosis after EA+RA treatment. EA+RA increased the intracellular ROS contents. EA+RA-induced apoptosis was accompanied by MMP attenuation and caspase-3/7 activation. EA+RA-induced differentiation was along with MEK/ERK and Akt activation and increased expression of PU.1, CCAAT/enhancer-binding protein ß (C/EBPß) and C/EBPε. N-acetyl-L-cysteine (NAC), an antioxidant, thoroughly reduced EA+RA-increased ROS, and also inhibited MMP attenuation, the activation of caspase- 3/7, MEK/ERK and Akt pathways, the elevation of PU.1 and C/EBPs, and apoptosis and differentiation. However, MEK or PI3K specific inhibitors only suppressed EA+RA-triggered differentiation and the elevation of PU.1 and C/EBPs, but not ROS levels. CONCLUSION: EA+RA induced cell apoptosis through ROS dependent MMP attenuation and caspase 3/7 activation while inducing differentiation by ROS-MEK/ERK-PU.1/C/EBPs and ROS-Akt-PU.1/C/EBPs pathways. In summary, it may provide innovative ATRA-based combination therapy strategies for AML patients via ROS.
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Antineoplásicos , Apoptose , Diferenciação Celular , Ensaios de Seleção de Medicamentos Antitumorais , Ácido Etacrínico , Leucemia Mieloide Aguda , Espécies Reativas de Oxigênio , Tretinoína , Humanos , Apoptose/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Tretinoína/farmacologia , Tretinoína/química , Diferenciação Celular/efeitos dos fármacos , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/patologia , Leucemia Mieloide Aguda/metabolismo , Ácido Etacrínico/farmacologia , Ácido Etacrínico/química , Antineoplásicos/farmacologia , Antineoplásicos/química , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Estrutura Molecular , Proliferação de Células/efeitos dos fármacos , Relação Estrutura-Atividade , Células Tumorais CultivadasRESUMO
Prenatal cell-free DNA (cfDNA) screening uses extracellular fetal DNA circulating in the peripheral blood of pregnant women to detect prevalent fetal chromosomal anomalies. However, numerous severe conditions with underlying single-gene defects are not included in current prenatal cfDNA screening. In this prospective, multicenter and observational study, pregnant women at elevated risk for fetal genetic conditions were enrolled for a cfDNA screening test based on coordinative allele-aware target enrichment sequencing. This test encompasses the following three of the most frequent pathogenic genetic variations: aneuploidies, microdeletions and monogenic variants. The cfDNA screening results were compared to invasive prenatal or postnatal diagnostic test results for 1,090 qualified participants. The comprehensive cfDNA screening detected a genetic alteration in 135 pregnancies with 98.5% sensitivity and 99.3% specificity relative to standard diagnostics. Of 876 fetuses with suspected structural anomalies on ultrasound examination, comprehensive cfDNA screening identified 55 (56.1%) aneuploidies, 6 (6.1%) microdeletions and 37 (37.8%) single-gene pathogenic variants. The inclusion of targeted monogenic conditions alongside chromosomal aberrations led to a 60.7% increase (from 61 to 98) in the detection rate. Overall, these data provide preliminary evidence that a comprehensive cfDNA screening test can accurately identify fetal pathogenic variants at both the chromosome and single-gene levels in high-risk pregnancies through a noninvasive approach, which has the potential to improve prenatal evaluation of fetal risks for severe genetic conditions arising from heterogenous molecular etiologies. ClinicalTrials.gov registration: ChiCTR2100045739 .
Assuntos
Ácidos Nucleicos Livres , Teste Pré-Natal não Invasivo , Gravidez , Humanos , Feminino , Diagnóstico Pré-Natal/métodos , Estudos Prospectivos , Aneuploidia , Ácidos Nucleicos Livres/genéticaRESUMO
The quality standards for Andrographis paniculata, a widely used medicinal herb, exhibited significant variations across different pharmacopeias. In this study, we compared the HPLC content determination methods and total lactone content of A. paniculata samples from different regions, as specified in the Chinese (CP), United States (USP), European (EP), Thai (TP), and Indian pharmacopeias (IP), as well as the Hong Kong Chinese Materia Medica Standards (HK). We aimed to assess the differences and similarities among these pharmacopeias and harmonized international quality standards for A. paniculata. The analysis revealed variations in sample preparation, liquid chromatographic conditions, fingerprint profiles, and total lactone content among the different pharmacopeias. Specifically, the CP and HK methods exhibited superior sample preparation and chromatographic separation. Further comparing the content of 20 A. paniculata samples with the CP, USP, EP and HK methods showed consistent determinations for the same components, indicating similar detection capabilities. The discrepancies in total lactone content primarily stemmed from differences in the number and types of detected compounds. Moreover, the acceptance criteria exhibited a stringency in the order CP > HK > EP > USP. In conclusion, this comparison analysis of content determination in CP, USP, HK, EP, TP and IP provided a scientific foundation for the international standardization and trade regulations of A. paniculata. It also served as a valuable reference for the development of international quality standards for other medicinal herbs, facilitating the harmonization of global pharmaceutical standards.