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Objective: To investigate the effects of lncRNA SNHG11 on proliferation, migration, invasion and apoptosis of colorectal cancer cancer cells and possible mechanisms. Methods: qRT-PCR was performed to detect the expression level of lncRNA SNHG11 in colorectal cancer tissues and its related cell lines. The correlation between SNHG11 expression and clinical prognosis of patients was assessed by bioinformatics techniques. Cultured CRC cell lines were transfected with shCtrl (shCtrl group), shSNHG11#1 (shSNHG11#1 group), shSNHG11#2 (shSNHG11#2 group), Control cDNA (Control cDNA group), and SNHG11 cDNA (SNHG11 cDNA), respectively. Thiazolyl blue (MTT), clone formation assay, Transwell assay, cell scratch assay, and flow cytometry were used to detect the proliferation, migration, invasion, and apoptosis of CRC cells in each group. Western protein blotting was used to detect the expression of relevant proteins in each group, and the effect of lncRNA SNHG11 knockdown on the growth of tumour cells in vivo was analysed by nude mice tumouring assay. Phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signalling pathway inhibitor LY294002 was used for rescue experiments. Results: The expression of lncRNA SNHG11 was significantly higher in colorectal cancer cells and tissues than in normal tissues (P<0.05). Survival analysis showed that the expression level of SNHG11 was not statistically associated with CRC survival (P>0.05). shSNHG11#2 group compared with shCtrl group. MTT OD490/570 values decreased, the number of CRC cell clones decreased, the number of Transwell cells decreased, the area of cell scratch decreased, and the apoptosis rate increased (P<0.05). The mesenchymal markers matrix metalloproteinase (MMP9), N-cadherin and vimentin were significantly reduced, and the expression of the epithelial marker E-cadherin was upregulated. The expression of anti-apoptotic proteins Bcl-2 and Bcl-xl was decreased, and the expression of pro-apoptotic protein Bax was increased (P<0.05).In vivo experiments showed that lncRNA SNHG11 knockdown inhibited the growth of colorectal cancer cells, and the expression of Ki67 was reduced in tumours (P<0.05). LncRNA SNHG11 knockdown inhibited the expression of p-PI3K, p-Akt and p-mTOR.The PI3K/Akt/mTOR signaling pathway inhibitor LY294002 was able to restore the malignant cytological progression of colorectal cancer cells induced by the overexpression of lncRNA SNHG11. Conclusions: LncRNA SNHG11 is highly expressed in colorectal cancer. lncRNA SNHG11 can promote the malignant progression of colorectal cancer cells by regulating the PI3K/Akt/mTOR signaling pathway, and this finding provides a new theoretical basis for targeted therapy of colorectal cancer.
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Neoplasias Colorrectales , ARN Largo no Codificante , Animales , Ratones , Humanos , Fosfatidilinositol 3-Quinasa/metabolismo , Fosfatidilinositol 3-Quinasa/farmacología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Fosfatidilinositol 3-Quinasas/genética , Fosfatidilinositol 3-Quinasas/metabolismo , Fosfatidilinositol 3-Quinasas/farmacología , ARN Largo no Codificante/genética , Ratones Desnudos , ADN Complementario/farmacología , Línea Celular Tumoral , Proliferación Celular , Transducción de Señal , Serina-Treonina Quinasas TOR/genética , Serina-Treonina Quinasas TOR/metabolismo , Serina-Treonina Quinasas TOR/farmacología , Neoplasias Colorrectales/genética , Mamíferos/genética , Mamíferos/metabolismoRESUMEN
Refractive error is a common ophthalmic disease in children. It refers to the mismatch between the axial length and the refractive power that results in visual blur, which is usually driven by the interaction of genetic and environmental factors. The impacts of pregnancy and puerperium-related factors on refractive error in children have gradually gained attention. According to the different stages of pregnancy, this review summarizes the impacts of four aspects on refractive error in children, including lifestyle during pregnancy, complications and comorbidities during pregnancy, adverse pregnancy outcomes and other factors, which aims to provide perinatal healthcare clues for the prevention and control of refractive error in children, achieve prevention beforehand and reduce the public health burden of refractive error in children.
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Errores de Refracción , Niño , Femenino , Humanos , Embarazo , Refracción Ocular , Periodo PospartoRESUMEN
Objective: To understand the prevalence of occasional hypertension in preschool children in three provinces in the middle and lower reaches of the Yangtze River in China, and analyze the relationship between their sleep status and occasional hypertension. Methods: From October to November 2017, a total of 24 842 preschool children from 109 kindergartens in 11 cities in Hubei, Anhui and Jiangsu provinces were selected by intentional sampling method. A self-made questionnaire was used to collect basic information about the subjects, and the sleep status data was collected by the Children's Sleep Habits Questionnaire. Physical examinations were performed on the subjects, and height, weight and blood pressure were measured on-site. The difference in occasional hypertension detection rate among preschool children with different characteristics was compared, and the correlation between sleep status and occasional hypertension detection rate was analyzed by the multivariate logistic regression model. Results: The age of the subjects was (4.4±1.0) years, including 12 729 boys (51.2%). The prevalence of occasional hypertension was 31.8% (7 907/24 842). The prevalence of occasional hypertension among preschool children in three provinces of the middle and lower reaches of the Yangtze River was 31.8%. There were statistically significant differences in the detection rate of occasional hypertension among preschool children of different genders, age groups, family residence, family economic status and parents' education level (all P values<0.05). The detection rate of occasional hypertension in children with less than 10 hours of sleep was higher than those with sufficient sleep, and the difference was statistically significant (P<0.05). The results of multivariate logistic regression analysis showed that after adjusting for factors such as gender, age, family residence, family economic status, parental education level, parental smoking history, and physical constitution, the ORs (95%CI) for less than 10 hours of sleep, turning on the lights while sleeping, and poor sleep quality were 1.09 (1.03-1.15), 1.17 (1.07-1.28) and 1.04 (0.91-1.18), respectively, compared with the corresponding reference group. Conclusion: The detection rate of occasional hypertension is high in preschool children in the middle and lower reaches of the Yangtze River and there is a positive correlation between insufficient sleep and turning on the light when sleeping and occasional hypertension in preschool children.
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Hipertensión , Ríos , Humanos , Masculino , Preescolar , Femenino , Sueño , Hipertensión/epidemiología , Presión Sanguínea , China/epidemiologíaRESUMEN
The objectives of this retrospective observational study were to investigate the association between BCS at 21 d before calving with prepartum and postpartum DMI, energy balance (EB), and milk yield. Data from 427 multigravid cows from 11 different experiments conducted at the University of Florida (Gainesville, FL) were used. Cows were classified according to their BCS at 21 d before calving as fat (BCS ≥ 4.00; n = 83), moderate (BCS = 3.25-3.75; n = 287), and thin (BCS ≤ 3.00; n = 57). Daily DMI from -21 to -1 and from +1 to +28 DIM was individually recorded. Energy balance was calculated as the difference between net energy for lactation consumed and required. Dry matter intake in fat cows was lower than that in moderate and thin cows both prepartum (fat = 9.97 ± 0.21, moderate = 11.15 ± 0.14, and thin = 11.92 ± 0.22 kg/d) and postpartum (fat = 14.35 ± 0.49, moderate = 15.47 ± 0.38, and thin = 16.09 ± 0.47 kg/d). Dry matter intake was also lower for moderate cows compared with thin cows prepartum, but not postpartum. Energy balance in fat cows was lower than in moderate and thin cows both prepartum (fat = -4.16 ± 0.61, moderate = -1.20 ± 0.56, and thin = 0.88 ± 0.62 Mcal/d) and postpartum (fat = -12.77 ± 0.50, moderate = -10.13 ± 0.29, and thin = -6.14 ± 0.51 Mcal/d). Energy balance was also lower for moderate cows compared with thin cows both prepartum and postpartum. There was a quadratic association between BCS at 21 d before calving and milk yield. Increasing BCS from 2.5 to 3.5 was associated with an increase in daily milk yield of 6.0 kg and 28 d cumulative milk of 147 kg. Increasing BCS from 3.5 to 4.5 was associated with a decrease in daily milk yield of 4.4 kg and 28 d cumulative milk of 116 kg. In summary, a moderate BCS at 21 d before calving was associated with intermediate DMI and EB pre- and postpartum but greater milk yield compared with thinner and fatter cows. Our findings indicate that a moderate BCS is ideal for ensuring a successful lactation.
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Metabolismo Energético , Lactancia , Leche , Periodo Posparto , Animales , Bovinos , Femenino , Leche/metabolismo , Embarazo , Estudios Retrospectivos , Dieta/veterinariaRESUMEN
Surgical site infections (SSIs) are a common type of healthcare-associated infection. We performed a literature review to demonstrate the incidence of SSIs in mainland China based on studies since 2010. We included 231 eligible studies with ≥30 postoperative patients, comprising 14 providing overall SSI data regardless of surgical sites and 217 reporting SSIs for a specific site. We found that the overall SSI incidence was 2.91% (median; interquartile range: 1.05%, 4.57%) or 3.18% (pooled; 95% confidence interval: 1.85%, 4.51%) and the SSI incidence varied remarkably according to the surgical site between the lowest (median, 1.00%; pooled, 1.69%) in thyroid surgeries and the highest (median, 14.89%; pooled, 12.54%) in colorectal procedures. We uncovered that Enterobacterales and staphylococci were the most common types of micro-organisms associated with SSIs after various abdominal surgeries and cardiac or neurological procedures, respectively. We identified two, nine, and five studies addressing the impact of SSIs on mortality, the length of stay (LOS) in hospital, and additional healthcare-related economic burden, respectively, all of which demonstrated increased mortality, prolonged LOS, and elevated medical costs associated with SSIs among affected patients. Our findings illustrate that SSIs remain a relatively common, serious threat to patient safety in China, requiring more action. To tackle SSIs, we propose to establish a nationwide network for SSI surveillance using unified criteria with the aid of informatic techniques and to tailor and implement countermeasures based on local data and observation. We highlight that the impact of SSIs in China warrants further study.
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BACKGROUND: Film boiling occurs in the cooling process of samples with liquid nitrogen, which limits heat transfer and decreases the cooling rate. OBJECTIVE AND METHODS: The study developed a method to enhance convective heat transfer by wrapping the French straw (FS) with a layer of medical gauze upon cooling to eliminate film boiling. A numerical model was used to study the thermodynamic mechanism in the method. RESULTS: Numerical simulation based on heat transfer and crystallization equations indicated that wrapping the FS with medical gauze could suppress film boiling. Experimental verification showed the increased cooling rate and better cell survival when wrapped FS was used. CONCLUSION: Numerical simulation and experimental verification demonstrated the efficacy of wrapping FS with medical gauze for better cell cryopreservation. Doi.org/10.54680/fr23510110312.
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Criopreservación , Vitrificación , Calor , Transición de Fase , Supervivencia CelularRESUMEN
A molecular diagnostic assay which could be stored at room temperature was developed to rapidly detect Mycobacterium tuberculosis (MTB) based on loop-mediated isothermal amplification (LAMP) technology and dry-reagent process. LAMP uses 4 or 6 primers and Bst DNA polymerase to amplify DNA at a constant temperature. The results showed that the LAMP assay could detect the amplification of IS6110 target gene within 20 min using real-time fluorescence signal detection. The sensitive of LAMP assay was similar to the PCR technology while the precision of PCR was better than LAMP (coefficient of variation, LAMP 18.9%, PCR 3.4%), meaning LAMP was more suitable for qualitative detection. The LAMP assay did not amplify DNA of other 10 types of pathogens, including Neisseria meningitidis, Haemophilus influenzae, Staphylococcus aureus, Streptococcus pneumoniae, Rubivirus, mumps virus, adenovirus (type 3), adenovirus (type 7), respiratory syncytial virus B and parainfluenza virus type 2, indicating a good specificity. Furthermore, a dry-reagent assay was developed using air-drying and freeze-drying process. The performance of dried reagents did not change after 10 days storage at 50 â, meaning the dried reagents could be stored at room temperature (25 â) for more than six months. The dry-reagent LAMP assay also successfully amplified MTB DNA from several clinical samples within 20 min. In conclusion, the developed LAMP assay together with isothermal amplifier could rapidly detection MTB.
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Mycobacterium tuberculosis , Humanos , Mycobacterium tuberculosis/genética , Indicadores y Reactivos , Sensibilidad y Especificidad , Técnicas de Amplificación de Ácido Nucleico/métodos , ADNRESUMEN
To examine the effects of evaporative cooling on systemic and mammary inflammation of lactating dairy cows, 30 multiparous Holstein cows (parity = 2.4, 156 d in milk) were randomly assigned to 1 of 2 treatments: cooling (CL) with fans and misters or not (NC). The experiment was divided into a 10-d baseline when all cows were cooled, followed by a 36-d environmental challenge when cooling was terminated for NC cows. The onset of environmental challenge was considered as d 1. Temperature-humidity index averaged 78.4 during the environmental challenge. Milk yield and dry matter intake (DMI) were recorded daily. Blood and milk samples were collected from a subset of cows (n = 9/treatment) on d -3, 1, 3, 7, 14, and 28 of the experiment to measure cortisol, interleukin 10 (IL10), tumor necrosis factor-α (TNF-α), haptoglobin, and lipopolysaccharide binding protein (LBP). Mammary biopsies were collected from a second subset of cows (n = 6/treatment) on d -9, 2, 10, and 36 to analyze gene expression of cytokines and haptoglobin. A subset of cows (n = 7/treatment) who were not subjected to mammary biopsy collection received a bolus of lipopolysaccharides (LPS) in the left rear quarter on d 30 of the experiment. Blood was sampled from cows and milk samples from the LPS-infused quarter were collected at -4, 0, 3, 6, 12, 24, 48, and 96 h relative to infusion, for analyses of inflammatory products. Deprivation of cooling decreased milk yield and DMI. Compared with CL cows, plasma cortisol concentration of NC cows was higher on d 1 but lower on d 28 of the experiment (cooling × time). Deprivation of cooling did not affect circulating TNF-α, IL10, haptoglobin, or LBP. Compared with CL cows, NC cows tended to have higher milk IL10 concentrations but did not show effects in TNF-α, haptoglobin, or LBP. No differences were observed in mammary tissue gene expression of TNF-α, IL10, and haptoglobin. Milk yield declined after LPS infusion but was not affected by treatment. Compared with CL cows, NC cows had greater milk somatic cell count following intramammary LPS infusion. Non-cooled cows had lower circulating TNF-α and IL10 concentrations and tended to have lower circulating haptoglobin concentrations than CL cows. Milk IL10 and TNF-⺠concentrations were higher 3 h after LPS infusion for NC cows compared with CL cows. Additionally, NC cows tended to have higher milk haptoglobin concentration after LPS infusion than CL cows. In conclusion, deprivation of evaporative cooling had minimal effects on lactating cows' basal inflammatory status, but upregulated mammary inflammatory responses after intramammary LPS infusion.
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BACKGROUND: High-grade serous ovarian cancers (HGSCs) display a high degree of complex genetic alterations. In this study, we identified germline and somatic genetic alterations in HGSC and their association with relapse-free and overall survival. Using a targeted capture of 557 genes involved in DNA damage response and PI3K/AKT/mTOR pathways, we conducted next-generation sequencing of DNA from matched blood and tumor tissue from 71 HGSC participants. In addition, we performed the OncoScan assay on tumor DNA from 61 participants to examine somatic copy number alterations (SCNA). RESULTS: Approximately one-third of tumors had loss-of-function (LOF) germline (18/71, 25.4%) or somatic (7/71, 9.9%) variants in the DNA homologous recombination repair pathway genes BRCA1, BRCA2, CHEK2, MRE11A, BLM, and PALB2. LOF germline variants also were identified in other Fanconi anemia genes and in MAPK and PI3K/AKT/mTOR pathway genes. Most tumors harbored somatic TP53 variants (65/71, 91.5%). Using the OncoScan assay on tumor DNA from 61 participants, we identified focal homozygous deletions in BRCA1, BRCA2, MAP2K4, PTEN, RB1, SLX4, STK11, CREBBP, and NF1. In total, 38% (27/71) of HGSC patients harbored pathogenic variants in DNA homologous recombination repair genes. For patients with multiple tissues from the primary debulking or from multiple surgeries, the somatic mutations were maintained with few newly acquired point mutations suggesting that tumor evolution was not through somatic mutations. There was a significant association of LOF variants in homologous recombination repair pathway genes and high-amplitude somatic copy number alterations. Using GISTIC analysis, we identified NOTCH3, ZNF536, and PIK3R2 in these regions that were significantly associated with an increase in cancer recurrence and a reduction in overall survival. CONCLUSIONS: From 71 patients with HGCS, we performed targeted germline and tumor sequencing and provided a comprehensive analysis of these 557 genes. We identified germline and somatic genetic alterations including somatic copy number alterations and analyzed their associations with relapse-free and overall survival. This single-site long-term follow-up study provides additional information on genetic alterations related to occurrence and outcome of HGSC. Our findings suggest that targeted treatments based on both variant and SCNA profile potentially could improve relapse-free and overall survival.
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Neoplasias Ováricas , Humanos , Femenino , Neoplasias Ováricas/patología , Estudios de Seguimiento , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , Recurrencia Local de Neoplasia , Genómica , Serina-Treonina Quinasas TORRESUMEN
OBJECTIVES: Previous studies revealed that tooth loss or edentulism was related to mortality. However, research in developing countries with large numbers of elderly populations is rare, and whether sex differences exist in this relationship is unknown. This study aimed to investigate the association between edentulism and 7-year all-cause mortality among older adults in China and whether sex differences existed. STUDY DESIGN: This was a prospective cohort study. METHODS: Data were from 2011 to 2018 waves of the China Health and Retirement Longitudinal Study. A total of 6538 participants aged ≥60 years were included. Logistic models were adopted to estimate the risks of mortality according to edentulism. RESULTS: The participants with edentulism at baseline were 20% more likely to die over 7 years after controlling for a set of covariates (odds ratio [OR] = 1.20, 95% confidence interval [CI]: 1.02-1.42). Moreover, edentulism was associated with a 35% higher odds of death among male participants (OR = 1.35, 95% CI: 1.08-1.70), whereas a significant association was not found in female participants. CONCLUSIONS: The findings demonstrated that baseline edentulism predicted all-cause mortality in Chinese older adults, and sex differences existed in this association. This study implied the importance of developing oral health education programs, incorporating dietary recommendations into dental care for edentulous patients, and expanding the coverage of dental services in the health insurance system to prevent edentulism and alleviate its negative outcomes for older adults.
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Boca Edéntula , Anciano , Femenino , Humanos , Masculino , Pueblos del Este de Asia , Estudios Longitudinales , Boca Edéntula/epidemiología , Boca Edéntula/etiología , Estudios Prospectivos , Factores SexualesRESUMEN
OBJECTIVE: Esophageal cancer (EC) is a highly malignant digestive system tumor that often lacks evident early symptoms and has a poor prognosis. Pyroptosis, a form of programmed cell death, has been shown to be associated with the occurrence and progression of many malignancies. However, its role in esophageal cancer remains unclear. This work aimed to evaluate the prognostic value of pyroptosis-related genes (PRGs) in EC using data from The Cancer Genome Atlas (TCGA) cohort. MATERIALS AND METHODS: The RNA-seq data from 171 esophageal samples in the TCGA database were employed. Differential expression genes (DEGs) between tumor and non-tumor samples were compared. Protein-protein interaction (PPI) networks were constructed using the STRING database, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment and Gene Ontology (GO) analyses were performed using the "clusterProfiler" package in R. Furthermore, based on the DEGs, all esophageal cancer cases were classified into three subtypes. A risk model for gene features was established using the LASSO regression method, and EC patients in the TCGA cohort were divided into high-risk and low-risk groups. RESULTS: A total of 614 PRGs were identified. Among them, 32 DEGs (31 upregulated and 1 downregulated) were found between normal esophageal tissue and EC tissue. PPI analysis identified key genes including IL-1ß, CASP1, AIM2, HMGB1, GSDMD, PYCARD, IL-18, BAK1, and TP53. On the other hand, the low-risk group exhibited a significantly higher survival rate than the high-risk group (p < 0.001). Combined with the clinical characteristics of the TCGA cohort, it was found that the risk score was an independent prognostic factor for overall survival (OS) prediction in EC patients. KEGG and GO analyses revealed the enrichment of genes associated with cell proliferation in the high-risk group. CONCLUSIONS: PRGs play a crucial role in the occurrence and development of EC and can be used to predict the prognosis of EC patients.
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Neoplasias Esofágicas , Piroptosis , Humanos , Piroptosis/genética , Pronóstico , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/genética , Apoptosis , Caspasa 1RESUMEN
Parturition and dry-off are challenging events for dairy cows partially due to changes in endocrine responses. The aim of this experiment was to evaluate blood concentrations of cortisol and prolactin and their effects on proliferation of peripheral blood mononuclear cells (PBMC) with or without stimulation by common immune cell mitogens (lipopolysaccharide [LPS], and concanavalin A [ConA]) of multiparous dairy cows from late lactation to the dry period and from the dry period to early lactation. Two groups of cows were enrolled: cows from late lactation to the dry period enrolled at 8 d before dry-off (LTD, n = 6, days in milk at dry-off = 332 ± 41 d) and cows from the dry period to early lactation enrolled at 7 d before expected calving date (DTL, n = 7). Blood was collected on d -8, 3, 7, and 15 relatives to dry-off for LTD cows, and on d -7, 3, 7, and 21 relatives to calving for DTL cows to analyze circulating stress hormones and to isolate PBMC. The PBMC were stimulated in vitro with prolactin (PRL), hydrocortisone (HDC), LPS, ConA, PRL + LPS, PRL + ConA, HDC+LPS, and HDC + ConA to assess proliferative responses. Plasma cortisol and PRL concentrations of LTD and DTL cows were not affected by time. Regardless of time, addition of HDC reduced PBMC proliferation stimulated by LPS, but PRL had no effect. No time effect was observed for proliferation of PBMC collected from LTD cows, but PBMC collected at 21 d after calving had higher proliferative responses to LPS and ConA than those from late dry period or early lactation. In conclusion, results from this experiment confirmed the lower PBMC proliferation during the transition period from the final week of gestation to early lactation and suggested that cows transitioning from late lactation to dry period maintained unchanged cell-mediated immune function.
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Leucocitos Mononucleares , Prolactina , Femenino , Bovinos , Animales , Hidrocortisona , Lipopolisacáridos/farmacología , Lactancia/fisiología , LecheRESUMEN
OBJECTIVE: To evaluate the therapeutic effects of two therapeutic strategies based on metformin hydrochloride/vildagliptin and liraglutide on type 2 diabetes mellitus (T2DM) in obese patients. METHODS: We retrospectively collected the clinical data of 107 obese patients (BMI>25 kg/m2) with T2DM treated in Second Affiliated Hospital of Wannan Medical College (Wuhu, China) during 2019-2021, including 53 patients treated continuously with metformin hydrochloride/vildagliptin and 54 with liraglutide for 3 months. The changes in BMI, waist circumference, fasting blood glucose (FBG), postprandial blood glucose, HbA1C, fasting C-peptide, postprandial C-peptide, fasting insulin and postprandial insulin of the patients after treatment were compared between the two groups. RESULTS: In both of the groups, the patients all showed significant reductions of BMI, waist circumference, FBG, postprandial blood glucose and HbA1C (all P < 0.05) with improved fasting and postprandial C-peptide levels after the treatments (P < 0.05). The two treatment regimens showed comparable blood glucoselowering effects, but liraglutide produced better effect in reducing waist circumference (P < 0.01). Neither of two regimens obviously affected insulin level of the patients (P>0.05). CONCLUSION: Both metformin hydrochloride/vildagliptin and liraglutide have good therapeutic effects on T2DM in obese patients and can achieve good blood glucose and weight control, but liraglutide has a better effect for weight control.
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Diabetes Mellitus Tipo 2 , Metformina , Humanos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Metformina/uso terapéutico , Liraglutida/uso terapéutico , Vildagliptina , Hipoglucemiantes/uso terapéutico , Glucemia , Hemoglobina Glucada , Péptido C , Estudios Retrospectivos , Obesidad/tratamiento farmacológico , Resultado del Tratamiento , Quimioterapia CombinadaRESUMEN
Background High-grade serous ovarian cancers (HGSCs) display a high degree of complex genetic alterations. In this study, we identified germline and somatic genetic alterations in HGSC and their association with relapse-free and overall survival. Using a targeted capture of 577 genes involved in DNA damage response and PI3K/AKT/mTOR pathways, we conducted next-generation sequencing of DNA from matched blood and tumor tissue from 71 HGSC participants. In addition, we performed the OncoScan assay on tumor DNA from 61 participants to examine somatic copy number alterations. Results Approximately one-third of tumors had loss-of-function germline (18/71, 25.4%) or somatic (7/71, 9.9%) variants in the DNA homologous recombination repair pathway genes BRCA1, BRCA2, CHEK2, MRE11A, BLM , and PALB2 . Loss-of-function germline variants also were identified in other Fanconi anemia genes and in MAPK and PI3K/AKT/mTOR pathway genes. Most tumors harbored somatic TP53 variants (65/71, 91.5%). Using the OncoScan assay on tumor DNA from 61 participants, we identified focal homozygous deletions in BRCA1, BRCA2, MAP2K4, PTEN, RB1, SLX4, STK11, CREBBP , and NF1 . In total, 38% (27/71) of HGSC patients harbored pathogenic variants in DNA homologous recombination repair genes. For patients with multiple tissues from the primary debulking or from multiple surgeries, the somatic mutations were maintained with few newly acquired point mutations suggesting that tumor evolution was not through somatic mutations. There was a significant association of loss-of-function variants in homologous recombination repair pathway genes and high-amplitude somatic copy number alterations. Using GISTIC analysis, we identified NOTCH3, ZNF536 , and PIK3R2 in these regions that were significantly associated with an increase in cancer recurrence and a reduction in overall survival. Conclusions From 71 patients with HGCS, we performed targeted germline and tumor sequencing and provided a comprehensive analysis of these 577 genes. We identified germline and somatic genetic alterations including somatic copy number alterations and analyzed their associations with relapse-free and overall survival. This single-site long-term follow-up study provides additional information on genetic alterations related to occurrence and outcome of HGSC. Our findings suggest that targeted treatments based on both variant and SCNA profile potentially could improve relapse-free and overall survival.
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Objective: To investigate the rate of periprosthetic joint infection (PJI) revision surgeries and clinical information of hip-/knee- PJI cases nationwide from 2015 to 2017 in China. Methods: An epidemiological investigation. A self-designed questionnaire and convenience sampling were used to survey 41 regional joint replacement centers nationwide from November 2018 to December 2019 in China. The PJI was diagnosed according to the Musculoskeletal Infection Association criteria. Data of PJI patients were obtained by searching the inpatient database of each hospital. Questionnaire entries were extracted from the clinical records by specialist. Then the differences in rate of PJI revision surgery between hip- and knee- PJI revision cases were calculated and compared. Results: Total of 36 hospitals (87.8%) nationwide reported data on 99 791 hip and knee arthroplasties performed from 2015 to 2017, with 946 revisions due to PJI (0.96%). The overall hip-PJI revision rate was 0.99% (481/48 574), and it was 0.97% (135/13 963), 0.97% (153/15 730) and 1.07% (193/17 881) in of 2015, 2016, 2017, respectively. The overall knee-PJI revision rate was 0.91% (465/51 271), and it was 0.90% (131/14 650), 0.88% (155/17 693) and 0.94% (179/18 982) in 2015, 2016, 2017, respectively. Heilongjiang (2.2%, 40/1 805), Fujian (2.2%, 45/2 017), Jiangsu (2.1%, 85/3 899), Gansu (2.1%, 29/1 377), Chongqing (1.8%, 64/3 523) reported relatively high revision rates. Conclusions: The overall PJI revision rate in 34 hospitals nationwide from 2015 to 2017 is 0.96%. The hip-PJI revision rate is slightly higher than that in the knee-PJI. There are differences in revision rates among hospitals in different regions.
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Artroplastia de Reemplazo de Cadera , Artroplastia de Reemplazo de Rodilla , Infecciones Relacionadas con Prótesis , Humanos , Infecciones Relacionadas con Prótesis/epidemiología , Infecciones Relacionadas con Prótesis/diagnóstico , China/epidemiología , Hospitales , Reoperación , Estudios RetrospectivosRESUMEN
The 3D edge-enhancing gradient-echo (EDGE) MR imaging sequence offers superior contrast-to-noise ratio in the detection of focal cortical dysplasia. EDGE could benefit from 7T MR imaging but also faces challenges such as image inhomogeneity and low acquisition efficiency. We propose an EDGE-MP2RAGE sequence that can provide both EDGE and T1-weighted contrast, simultaneously, improving data-acquisition efficiency. We demonstrate that with sequence optimization, EDGE images with sufficient uniformity and T1-weighted images with high gray-to-white matter contrast can be achieved.
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Epilepsia , Sustancia Blanca , Humanos , Imagen por Resonancia Magnética/métodos , Sustancia Gris , Epilepsia/diagnóstico por imagen , Corteza Cerebral , Encéfalo/diagnóstico por imagenRESUMEN
Saccharomyces cerevisiae fermentation products are commonly used in dairy cattle ration to improve production efficiency and health. However, whether these benefits will persist during feed-restriction-induced negative energy balance is unknown. The objective of this experiment was to examine the effect of a Saccharomyces cerevisiae fermentation product (NT, NutriTek, Diamond V) on performance, metabolic, inflammatory, and immunological responses to a feed-restriction challenge in mid-lactation dairy cows. Sixty Holstein cows were blocked by parity, days in milk, and milk yield and then randomly assigned to 1 of the 2 supplements: NT or placebo (CTL). The supplements were mixed in total mixed ration before feeding at a rate of 19 g/d per cow. The production phase of the experiment lasted 12 wk. Intake and milk yield were recorded daily, and milk composition was measured weekly. After the production trial, a subset of cows (NT: n = 16; CTL: n = 16) were immediately enrolled in a 5-d feed-restriction challenge with 40% ad libitum intake followed by a 5-d realimentation. Milk yield and composition were measured at each milking from d -2 to 10 relative to feed restriction. Blood samples were collected on d -2, -1, 1, 2, 3, 4, 5, 6, 8, and 10 relative to the initiation of feed restriction to measure circulating metabolites, insulin, cortisol, IL-10, tumor necrosis factor-α, lipopolysaccharide binding protein, and haptoglobin. Immune function assessments, including peripheral mononuclear cell proliferation and functional assays of circulating granulocytes, were performed on d -3 and 4 of the feed restriction. No differences were observed in dry matter intake, milk yield, or concentrations or yield of components except for fat yield. An interaction of parity and treatment was observed for milk fat yield that was lower for CTL than NT in primiparous cows, but no differences were observed among treatments in milk fat yield of multiparous cows. Feed restriction successfully induced negative energy balance and its associated metabolic changes, including reduced concentrations of plasma glucose and increased nonesterified fatty acids and ß-hydroxybutyrate. Cows fed NT had a similar decrease in milk yield but had a more pronounced reduction in plasma glucose concentration and greater ß-hydroxybutyrate concentration during feed restriction than those fed CTL. Feed restriction did not induce evidence of systemic inflammation but did reduce granulocyte functional activity. Compared with CTL, feeding NT improved the reactive oxygen species production by granulocytes after stimulation by extracellular antigens. In conclusion, feeding NT increased milk fat production of first-lactation cows but did not affect overall productive performance. However, supplementation with NT improved induced granulocyte oxidative burst. This may explain the greater glucose utilization by cows fed NT rather than CTL during feed restriction.
Asunto(s)
Glucemia , Saccharomyces cerevisiae , Embarazo , Femenino , Bovinos , Animales , Fermentación , Saccharomyces cerevisiae/metabolismo , Ácido 3-Hidroxibutírico , Glucemia/metabolismo , Dieta/veterinaria , Lactancia/fisiología , Leche/química , Alimentación Animal/análisisRESUMEN
Objective: To investigate the current situation of cell phone use and sleep quality among college students, establish a sleep quality trajectory model and explore the influence of cell phone use on the sleep quality trajectory. Methods: Based on data from the College Student Behavior and Health Cohort Study 2019-2020, a latent class growth modeling was used to establish a sleep quality trajectory model among college students. The baseline influencing factors of sleep quality trajectories among college students were analyzed by χ2 test, and the effects of cell phone use on sleep quality trajectories were analyzed by binary logistic regression. Results: A total of 1 092 college students were included in the analysis. The detection rates of cell phone use and poor sleep quality were 24.5% and 13.3%. Latent class growth model identified two groups of sleep quality trend trajactories: an improved sleep quality group (86.0%) and a decreased sleep quality group (14.0%). The result of binary logistic regression showed that the cell phone use was a risk factor of sleep quality trajectories. Conclusion: The cell phone use during college period could increase the risk of poor sleep quality. Targeted intervention measures about cell phone use should be adopted to improve the sleep quality among college students.