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1.
BMC Med Genet ; 21(1): 214, 2020 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-33129265

RESUMO

BACKGROUND: Kyphoscoliotic Ehlers-Danlos syndrome (kEDS) is a rare autosomal recessive connective tissue disorder characterized by progressive kyphoscoliosis, congenital muscular hypotonia, marked joint hypermobility, and severe skin hyperextensibility and fragility. Deficiency of lysyl hydroxylase 1 (LH1) due to mutations of PLOD1 (procollagen-lysine, 2-oxoglutarate 5-dioxygenase 1) gene has been identified as the pathogenic cause of kEDS (kEDS-PLOD1). Up to now, kEDS-PLOD1 has not been reported among Chinese population. CASE PRESENTATION: A 17-year-old Chinese male patient presenting with hypotonia, joint hypermobility and scoliosis was referred to our hospital. After birth, he was found to have severe hypotonia leading to delayed motor development. Subsequently, joint hypermobility, kyphoscoliosis and amblyopia were found. Inguinal hernia was found at age 5 years and closed by surgery. At the same time, he presented with hyperextensible and bruisable velvety skin with widened atrophic scarring after minor trauma. Dislocation of elbow joint was noted at age of 6 years. Orthopedic surgery for correction of kyphoscoliosis was performed at age 10 years. His family history was unremarkable. Physical examination revealed elevated blood pressure. Slight facial dysmorphologies including high palate, epicanthal folds, and down-slanting palpebral fissures were found. He also had blue sclerae with normal hearing. X-rays revealed severe degree of scoliosis and osteopenia. The Echocardiography findings were normal. Laboratory examination revealed a slightly elevated bone turnover. Based on the clinical manifestations presented by our patient, kEDS was suspected. Genetic analysis revealed a novel homozygous missense mutation of PLOD1 (c.1697 G > A, p.C566Y), confirming the diagnosis of kEDS-PLOD1. The patient was treated with alfacalcidol and nifedipine. Improved physical strength and normal blood pressure were reported after 12-month follow-up. CONCLUSIONS: This is the first case of kEDS-PLOD1 of Chinese origin. We identified one novel mutation of PLOD1, extending the mutation spectrum of PLOD1. Diagnosis of kEDS-PLOD1 should be considered in patients with congenital hypotonia, progressive kyphoscoliosis, joint hypermobility, and skin hyperextensibility and confirmed by mutation analysis of PLOD1.

2.
Int J Nurs Stud ; 114: 103809, 2020 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-33207297

RESUMO

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a public health emergency of international concern and has caused traumatic experience for nurses worldwide. However, the prevalence of depression and anxiety symptoms in nurses, and how psychosocial factors influence nurses in this public crisis are unknown. OBJECTIVES: To determine the effect of COVID-19 on the mental health of nurses and the prevalence of anxiety and depression symptoms among nurses in China during the outbreak. DESIGN: A cross-sectional study. SETTINGS AND PARTICIPANTS: A total of 3,228 nurses in Sichuan Province and Wuhan City were selected by convenience sampling. All participants were invited to complete the questionnaire through WeChat from January 27 to February 3, 2020. METHODS: A self-reported questionnaire combining depression and anxiety scale was used to collect data anonymously. Binary and multivariate logistic regression was applied to measure the odds of psychosocial factors of anxiety and depression and perceived health, respectively. RESULTS: The total incidence of depression (34.3%) and anxiety (18.1%) during the COVID-19 outbreak was lower than that during the SARS outbreak; however, the rate of depression in our study (47.1%) was high and similar in a recent study (50.4%) about the health care workers exposed to COVID-19 in China. The results indicated that COVID-19-related stress, relationship quality with family, and demographic characteristics were associated with depression, anxiety, and perceived health status. Furthermore, the prevalence of depression was similar between nurses working in low-risk COVID-19 wards was as high as working in high-risk COVID-19 wards (OR, 1.078; 95% CI, 0.784-1.481). CONCLUSIONS: Our study revealed the high prevalence of depression and anxiety among nurses during the outbreak of COVID-19. COVID-19 factors and psychosocial factors were associated with mental health of nurses. The results suggest that hospitals should implement effective mental health promotion programs focused on occupational safety and family support to improve the well-being of nurses.

3.
Mol Genet Genomic Med ; : e1525, 2020 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-33166085

RESUMO

BACKGROUND: Osteogenesis imperfecta (OI) is a phenotypically and genetically heterogeneous bone disease characterized by bone fragility and recurrent fractures. X-linked inherited OI with mutation in PLS3 is so rare that its genotype-phenotype characteristics are not available. METHODS: We designed a novel targeted next-generation sequencing (NGS) panel with the candidate genes of OI to detect pathogenic mutations and confirmed them by Sanger sequencing. The phenotypes of the patients were also investigated. RESULTS: The proband, a 12-year-old boy from a nonconsanguineous family, experienced multiple fractures of long bones and vertebrae and had low bone mineral density (BMD Z-score of -3.2 to -2.0). His younger brother also had extremity fractures. A novel frameshift mutation (c.1106_1107insGAAA; p.Phe369Leufs*5) in exon 10 of PLS3 was identified in the two patients, which was inherited from their mother who had normal BMD. Blue sclerae were the only extraskeletal symptom in all affected individuals. Zoledronic acid was beneficial for increasing BMD and reshaping the compressed vertebral bodies of the proband. CONCLUSION: We first identify a novel mutation in PLS3 that led to rare X-linked OI and provide practical information for the diagnosis and treatment of this disease.

4.
Crit Rev Biotechnol ; : 1-14, 2020 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-33153325

RESUMO

As an important semi-essential amino acid, l-arginine is extensively used in the food and pharmaceutical fields. At present, l-arginine production depends on cost-effective, green, and sustainable microbial fermentation by using a renewable carbon source. To enhance its fermentative production, various metabolic engineering strategies have been employed, which provide valid paths for reducing the cost of l-arginine production. This review summarizes recent advances in molecular biology strategies for the optimization of l-arginine-producing strains, including manipulating the principal metabolic pathway, modulating the carbon metabolic pathway, improving the intracellular biosynthesis of cofactors and energy usage, manipulating the assimilation of ammonia, improving the transportation and membrane permeability, and performing biosensor-assisted high throughput screening, providing useful insight into the current state of l-arginine production.

5.
Exp Biol Med (Maywood) ; : 1535370220966253, 2020 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-33175607

RESUMO

Long non-coding RNAs are a kind of endogenous ncRNAs with a length of more than 200 bp. Accumulating evidence suggests that long non-coding RNAs function as pivotal regulators in tumorigenesis and progression. However, their biological roles in breast cancer remain largely unknown. Here, we found that IGF2 antisense RNA (IGF2-AS) was significantly decreased in breast cancer tissues, cell lines, and plasma. Patients with low IGF2-AS were more likely to develop larger tumor size and later clinical stage. Overexpression of IGF2-AS evidently inhibited the proliferation and induced apoptosis of MCF-7 and T47D cells in vitro, as well as retarded tumor growth in vivo. Further investigation revealed that IGF2-AS inhibited the expression of its sense-cognate gene IGF2 in an epigenetic DNMT1-dependent manner, resulting in the inactivation of downstream oncogenic PI3K/AKT/mTOR signaling pathway. Enforced expression of IGF2 could significantly block the tumor inhibitory effect of IGF2-AS. Importantly, we found that IGF2-AS could be used as an effective biomarker for breast cancer diagnosis and prognosis. Taken together, our study indicates that IGF2-AS is a tumor suppressor in breast cancer, restoration of IGF2-AS may be a promising treatment for this fatal disease.

6.
Artigo em Inglês | MEDLINE | ID: mdl-33175426

RESUMO

OBJECTIVE: The study aims to investigate the factors causing the difference of stroke patients' in-hospital cost and study these factors on health outcome in terms of mortality. METHODS: Eight hundred and sixty-two in-patients with stroke in a tertiary hospital in China from 2017 to 2019 were included in the database. Descriptive statistics indexes were used to describe patients' in-hospital cost and mortality. Based on Elixhauser coding algorithms, multiple linear regression and logistic regressions (LRs) were used to evaluate the impact of factors identified from univariate analysis on in-hospital cost and mortality, respectively. In addition to LRs, a comparison study was then carried out with random forest, gradient boosting decision tree and artificial neural network. RESULTS: Factors affecting both cost and mortality are age, discharged day-of-week, length of stay, stroke subtype, other neurological disorders, renal failure, fluid and electrolyte disorders and total number of comorbidities. CONCLUSION: With the increase of age, the mortality rate of in-patients (except for the juvenile) with stroke increases and the cost of hospitalization decreases. Intracerebral haemorrhage is the most devastating stroke for its highest mortality in short length of stay. Medical services should focus on these specific comorbidities.

7.
Artigo em Inglês | MEDLINE | ID: mdl-33166187

RESUMO

Patients with type 2 diabetes mellitus (T2DM) have a high risk of developing cholecystic disease. The gut microbiome has been shown to be strongly associated with cholecystectomy and T2DM pathogenesis. However, alterations of gut microbiome in T2DM patients undergone cholecystectomy remains unexplored. In this study, the gut microbiomes of 14 long-term T2DM patients who had undergone cholecystectomy (T2DIIC group) and 21 age- and/or sex-matched subjects with new-onset (T2DI group) and long-term (T2DII group) T2DM without cholecystectomy were assessed using 16S rRNA gene sequencing of stool samples. It was found that cholecystectomy could alleviate the decrease in Pielou's evenness and the increase in the relative abundances of the Firmicutes phylum and Lachnospira genus in long-term T2DM patients compared with that observed in the T2DII subjects. Moreover, cholecystectomy also significantly increased the relative abundance of the Fusobacteria phylum, as well as that of the Fusobacterium and Bilophila genera. Interestingly, the T2DIIC and T2DI groups showed higher similarities than was observed in the T2DII group with respect to patterns of gut microbiome composition and predicted gut metagenomes. In summary, cholecystectomy could partially alleviate long-term diabetes-induced dysbiosis of the gut microbiome composition and function, but alterations in T2DM patient health warrant further study.

8.
Artigo em Inglês | MEDLINE | ID: mdl-33201657

RESUMO

As an important method to further improve the storage density of resistive memory, multistage resistive switching devices have become an important research direction. However, no stable and controllable multistage resistive switching device has been prepared, and the working mechanism is still unclear. Here, a sandwich-structured device is simply prepared by spin coating, with the work layer is the Bi2FeCrO6 thin film. The device can realize bidirectional controllable multistage resistive switching behavior, the biggest on/off ratio is 104, and it can maintain stability without attenuation at 100 times slow loop and 104 times pulse cycle. The analyzes showed that the charged ions formed by defects in the device migrated under the action of an external electric field lead to the Schottky barrier height reversible changed. Which is the key to cause multistage resistive switching behavior. This work is the first report about the voltage control of bidirectional adjustable multistage resistive switching behavior in the Bi2FeCrO6 thin film. The principle of generation is analyzed, and important ideas and insights are provided for the preparation and treatment of related multistage resistive problems.

9.
J Anal Toxicol ; 2020 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-33206981

RESUMO

Ethanol is one of the most commonly used and abused substances worldwide. Identifying whether the source of ethanol detected in corpses is ante-mortem ingestion or post-mortem generation is especially important for determining the cause of death, which remains a vibrant field of research. During the synthesis of ethanol in the putrefaction process of corpses, other small molecules such as acetaldehyde and n-propanol could also be produced. According to our prospective statistical analysis based on authentic samples from forensic cases, it is rational to suspect ethanol generation after death when the concentration of acetaldehyde detected in blood exceeds 0.14 mg/mL. Through in vitro simulation experiments, in addition to confirming that ethyl glucuronide and ethyl sulphate are reliable biomarkers of ante-mortem ingestion of ethanol, we propose that acetaldehyde is far more sensitive than n-propanol as a potential marker in the blood of corpses for post-mortem ethanol formation.

10.
Diagn Microbiol Infect Dis ; 99(2): 115229, 2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-33161239

RESUMO

The risk factors and outcomes of patients with bloodstream infections (BSIs) caused by Acinetobacter baumannii are major concerns in clinical therapy. Multicenter case-control studies were performed to compare the clinical characteristics of 47 A. baumannii BSI patients and 124 matched controls with nonbloodstream A. baumannii infections and the clinical and molecular characteristics of BSI survivors and nonsurvivors. Additionally, the mortality of BSIs was assessed. The clinical characteristics, including neutropenia, ICU admission prior to positive culture, primary infection in the central nervous system, and carbapenem use prior to positive culture, were independently associated with BSI caused by A. baumannii. The mortality of the BSI patients was significantly higher than that of the controls. A high Pitt bacteremia score was found to be an independent predictor of mortality in the BSI patients. The healthcare-associated factors, disease severity level, or antibiotic usage increased the risks of A. baumannii BSI and related mortality.

11.
Front Immunol ; 11: 565862, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33133078

RESUMO

Background: Most hospitalized preterm infants receive antibiotics in the first days of life to prevent or treat infections. Short-term, early antibiotic treatment may also prevent the microbiota-dependent gut inflammatory disorder, necrotizing enterocolitis (NEC). It remains a challenge to predict NEC, and a few early blood diagnostic markers exist. Using preterm pigs as model for infants, blood parameters and plasma proteins affected by early progression of NEC were profiled in preterm pigs subjected to oral, systemic, or no antibiotics after preterm birth. Methods: Preterm newborn pigs were treated with saline (CON) or antibiotics (ampicillin, gentamicin, and metronidazole) given enterally (ENT) or parenterally (PAR), and fed formula for 4 days to induce variable microbiome-dependent sensitivities to NEC. The gut was collected for macroscopic scoring of NEC lesions and blood for hematology, blood biochemistry, and LC/MS-based plasma proteomics. Statistical modeling was applied to detect plasma proteins affected by NEC and/or antibiotics. Results: Analyzed across different antibiotic regimens, NEC progression was associated with altered blood parameters and abundance of 89 plasma proteins that were functionally involved in extracellular membrane destruction, lipid metabolism, coagulopathy, and acute phase response. Large NEC-related changes were observed in abundance of RBP4, FGA, AHSG, C5, PTPRG, and A-1-antichymotrypsin 2, indicating potential serving as early markers of NEC. Conversely, antibiotic treatment, independent of NEC, affected only 4 proteins with main differences found between ENT and CON pigs. Conclusion: Early postnatal development of NEC lesions is associated with marked plasma protein changes that may be used for early NEC diagnosis.

12.
J Craniofac Surg ; 31(8): 2304-2309, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33136877

RESUMO

Three-dimensional (3D) technology including 3D reconstruction and 3D printing technology, has been widely used in clinical treatment, especially in surgical planning, and image navigation technology, which can make surgical procedures more accurate, now is also increasingly favored by surgeons. But the combination of those 2 technologies was rarely reported. Thus, this study will preliminarily investigate the feasibility and the effect of the combination of 2 technologies in endonasal skull base surgery. Eight patients were involved in this study (from October 2016 to July 2017 at The Affiliated Hospital of Qingdao University), 5 cases of nasal skull base tumors and 3 cases of foreign body perforation. All operations were done under the assistance of 3D technology and image guidance system. Surgical discussion with patient, preoperative planning and clinical teaching were investigated between 2D images and 3D models by voting. For all cases, 3D reconstruction model and 3D printed model were deemed to be more helpful than CT/MRI images in surgical discussion with the patient; surgical simulation on 3D model in preoperative planning was largely deemed to be helpful and very helpful; and in clinical teaching, 3D models combined with image guidance system were deemed to be more helpful in understanding the disease than using 2D images. Besides, all patients recovered well after surgery, no recurrence and complications were found in the follow-up. The combination of 3D technology and electromagnetic image guidance system could improve surgical efficiency and the quality of clinical teaching.

13.
Cell Death Dis ; 11(10): 860, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-33060563

RESUMO

GATA6 acts as an oncogene or tumour suppressor in different cancers. Previously, we found that aberrant expression of GATA6 promoted metastasis in cholangiocarcinoma (CCA). However, the mechanism by which GATA6 promotes metastasis in CCA is unclear. In the present study, we aimed to investigate the role of GATA6 in CCA cell epithelial-mesenchymal transition (EMT). Our results showed that GATA6 expression was positively associated with N-cadherin and vimentin expression but negatively associated with E-cadherin expression in 91 CCA samples. GATA6 promoted EMT and metastasis in CCA cells in vitro and in vivo based on knockdown and overexpression analyses. ChIP-sequencing data revealed that MUC1 is a novel downstream target of GATA6. GATA6 upregulated MUC1 expression through binding to both the 1584 and 1456 GATA-motifs in the promoter region and enhancing its transcription by luciferase reporter assays and point-mutant assays. MUC1 expression was positively associated with N-cadherin and vimentin expression but negatively associated with E-cadherin expression in 91 CCA samples. In addition, MUC1 promoted EMT in CCA cells based on knockdown and overexpression analyses. Moreover, MUC1 knockdown significantly abrogated the GATA6-induced EMT in CCA cells, indicating that MUC1 promoted EMT through upregulating MUC1 in CCA cells. ß-Catenin is a putative transcriptional coactivator that regulates EMT in cancers. Our data showed that MUC1 expression was positively associated with nuclear ß-catenin expression in 91 CCA samples. MUC1 upregulated nuclear ß-catenin expression in CCA cells. Moreover, MUC1 bound to ß-catenin in CCA cells based on protein immunoprecipitation analyses. MUC1 knockdown significantly decreased the binding of MUC1 to ß-catenin, and thereby decreased nuclear ß-catenin protein levels in CCA cells, indicating that MUC1 bound to ß-catenin and increased its nuclear expression in CCA cells. Together, our results show that GATA6 promotes EMT through MUC1/ß-catenin pathway in CCA, indicating potential implications for anti-metastatic therapy.

14.
BMJ Open ; 10(10): e039501, 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-33033030

RESUMO

OBJECTIVES: With a marginally effective vaccine and no significant breakthroughs in new treatments, a sensitive and specific method to distinguish active tuberculosis from latent tuberculosis infection (LTBI) would allow for early diagnosis and limit the spread of the pathogen. The analysis of multiple cytokine profiles provides the possibility to differentiate the two diseases. DESIGN: Systematic review and meta-analysis. DATA SOURCES: PubMed, Cochrane Library, Clinical Key and EMBASE databases were searched on 31 December 2019. ELIGIBILITY CRITERIA: We included case-control studies, cohort studies and randomised controlled trials considering IFN-γ, TNF-α, IP-10, IL-2, IL-10, IL-12 and VEGF as biomarkers to distinguish active tuberculosis and LTBI. DATA EXTRACTION AND SYNTHESIS: Two students independently extracted data and assessed the risk of bias. Diagnostic OR, sensitivity, specificity, positive and negative likelihood ratios and area under the curve (AUC) together with 95% CI were used to estimate the diagnostic value. RESULTS: Of 1315 records identified, 14 studies were considered eligible. IL-2 had the highest sensitivity (0.84, 95% CI: 0.72 to 0.92), while VEGF had the highest specificity (0.87, 95% CI: 0.73 to 0.94). The highest AUC was observed for VEGF (0.85, 95% CI: 0.81 to 0.88), followed by IFN-γ (0.84, 95% CI: 0.80 to 0.87) and IL-2 (0.84, 95% CI: 0.81 to 0.87). CONCLUSION: Cytokines, such as IL-2, IFN-γ and VEGF, can be utilised as promising biomarkers to distinguish active tuberculosis from LTBI. PROSPERO REGISTRATION NUMBER: CRD42020170725.

15.
Medicine (Baltimore) ; 99(40): e22488, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33019444

RESUMO

RATIONALE: Some acute myeloid leukemia (AML) patients present with features mimicking the classical hypergranular subtype of acute promyelocytic leukemia (APL) but without the typical promyelocytic leukemia/retinoic acid receptor α (PML/RARα) rearrangement. Herein, we report an AML patient resembling APL but with nucleoporin 98/retinoid acid receptor gamma gene (NUP98/RARG) fusion transcript and Runt-related transcription factor 1 (RUNX1) mutation. PATIENT CONCERNS: An 18-year-old male presented at the hospital with a diagnosis of AML. DIAGNOSES: The patient was diagnosed with bone marrow examination. Bone marrow smear displayed 90.5% promyelocytes. Fluorescence in situ hybridization analysis failed to detect the PML/RARα fusion transcript or RARα amplification. While real-time polymerase chain reaction showed positivity for the NUP98/RARG fusion transcript. G-banding karyotype analysis showed a normal karyotype. INTERVENTIONS: The patient showed resistance to arsenic trioxide and standard 3 + 7 chemotherapy, but eventually achieved complete remission through the Homoharringtonine, Cytarabine, and Aclarubicin chemotherapy. OUTCOMES: These measures resulted in a rapid response and disease control. LESSONS: Acute myeloid leukemia with the NUP98/RARG fusion gene and the RUNX1 mutation may be a special subtype of AML and may benefit from the alkaloid-based regimen.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Adolescente , Subunidade alfa 2 de Fator de Ligação ao Core/genética , Diagnóstico Diferencial , Humanos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Promielocítica Aguda/diagnóstico , Masculino , Complexo de Proteínas Formadoras de Poros Nucleares/genética , Receptores do Ácido Retinoico/genética
16.
Braz J Med Biol Res ; 53(11): e10068, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33053111

RESUMO

Diabetes mellitus (DM) has a high prevalence in patients with pancreatic cancer (PaC), but the prognostic value of DM in PaC remains controversial. Alterations of P-glycoprotein (P-gp) and cytochrome P450 3A4 (CYP3A4) contribute to multidrug resistance and intestinal metabolism in a variety of cancer types, which may be implicated in DM development. This study aimed to explore the potential prognostic value of P-gp and CYP3A4 in PaC patients in the context of DM through long-term follow-up. We retrospectively reviewed the medical records of patients with PaC admitted at The First People's Hospital of Changzhou, Jiangsu, China, from January 2011 to November 2019 and identified two cohorts of adult patients with PaC, including 24 with DM and 24 without DM (non-DM). The baseline clinical characteristics and outcomes were compared. Immunohistochemistry showed that protein expression of P-gp, but not CYP3A, in duodenum tissues was significantly upregulated in PaC patients with DM compared with those without DM. Kaplan-Meier analysis and log-rank test showed that the survival of patients with PaC and DM/high expression of P-gp was not significantly reduced compared with that of patients without DM/low expression of P-gp. These findings suggested that P-gp expression levels were different in the DM and non-DM groups of patients with PaC, but DM and duodenal P-gp levels were not associated with the long-term survival of patients with PaC. It appears that the presence of DM or P-gp expression levels may not serve as effective prognostic markers for PaC.

17.
Front Endocrinol (Lausanne) ; 11: 557050, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33101196

RESUMO

Purpose: The occurrence of parathyroid carcinoma (PC) and atypical parathyroid neoplasm (APN) in multiple endocrine neoplasia type 1 (MEN1) is rare. The present paper reports the cases of 3 MEN1-PC/APN patients at our center and discusses the prevalence in a Chinese MEN1 cohort. Methods: This report is a retrospective analysis of 153 MEN1-associated primary hyperparathyroidism (MEN1-HPT) patients at our center, which included 3 MEN1-associated PC/APN (MEN1-PC/APN) patients. The clinical manifestations, biochemical indices, pathological findings, and therapy have been summarized along with the report of the genetic testing of the 3 patients. Results: Of the 153 MEN1-HPT patients, 1 (0.7%) was histopathologically diagnosed with PC and 2 (1.3%) with APN. Three heterozygous mutations were identified in the 3 MEN1-PC/APN patients (c.917 T > G, c.431T > C, and c.549 G > C). The cumulative findings of 3 cases with 18 previously reported MEN1-PC/APN cases revealed that the mean serum calcium (Ca) level was 3.15 ± 0.44 mmol/L and the median parathyroid hormone (PTH) level was 327 pg/mL (214.1, 673.1), both of which were significantly higher as compared to the respective levels in non-PC/APN MEN1 patients at our center [Ca: 2.78 mmol/L [2.61, 2.88], PTH: 185.5 pg/mL [108.3, 297.0]; P = 0.0003, 0.0034, respectively]. Conclusion: MEN 1-PC/APN is a rare disease, with a prevalence of only 2.0% among the MEN1-HPT cohort at our center. The affected patients recorded higher serum Ca level and PTH levels than those with MEN1-associated benign tumors. However, the diagnosis of MEN1-PC/APN is based upon pathology most of the times.

18.
Arch Biochem Biophys ; 694: 108612, 2020 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-33007281

RESUMO

Apoptotic and inflammatory pathways play important roles in Mycobacterium tuberculosis-infected macrophages. Sirt1 is a member of the deacetylase family that is known to promote apoptosis resistance in mammalian cells and was recently reported to regulate mycobacterial immunopathogenesis via inflammatory responses. However, the apoptotic role of Sirt1 in the process of M. tuberculosis infection remains unclear. With the help of mouse peritoneal macrophage samples, we have shown that resveratrol, a Sirt1 activator, inhibited M. tuberculosis-induced apoptosis in peritoneal macrophages. Further, we found that Sirt1 activation prompted M. tuberculosis induced GSK3ß phosphorylation. Further investigation into the possible mechanisms of action showed that Sirt1 directly interacted with GSK3ß and enhanced GSK3ß phosphorylation by promoting its deacetylation. Sirt1 activation inhibited M. tuberculosis growth. Thus, it seemed that Sirt1 acted as a novel regulator of apoptosis signaling in M. tuberculosis infection via its direct effects on GSK3ß. Sirt1 may therefore be a new candidate for the prevention and treatment of tuberculosis.

19.
Sci Rep ; 10(1): 17899, 2020 10 21.
Artigo em Inglês | MEDLINE | ID: mdl-33087803

RESUMO

Triple-negative breast cancer (TNBC) accounts for 15-20% of breast cancer cases in the United States, lacks targeted therapeutic options, and is associated with a 40-80% risk of recurrence. Thus, identifying actionable targets in treatment-naïve and chemoresistant TNBC is a critical unmet medical need. To address this need, we performed high-throughput drug viability screens on human tumor cells isolated from 16 patient-derived xenograft models of treatment-naïve primary TNBC. The models span a range of TNBC subtypes and exhibit a diverse set of putative driver mutations, thus providing a unique patient-derived, molecularly annotated pharmacologic resource that is reflective of TNBC. We identified therapeutically actionable targets including kinesin spindle protein (KSP). The KSP inhibitor targets the mitotic spindle through mechanisms independent of microtubule stability and showed efficacy in models that were resistant to microtubule inhibitors used as part of the current standard of care for TNBC. We also observed subtype selectivity of Prima-1Met, which showed higher levels of efficacy in the mesenchymal subtype. Coupling pharmacologic data with genomic and transcriptomic information, we showed that Prima-1Met activity was independent of its canonical target, mutant p53, and was better associated with glutathione metabolism, providing an alternate molecularly defined biomarker for this drug.

20.
Medicine (Baltimore) ; 99(44): e22989, 2020 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-33126374

RESUMO

BACKGROUND: Cerebral hemorrhage (CH) is a very common cerebrovascular disorder in clinical practice. More and more studies reported that proper nursing care could promote the rate of treatment, and improve the prognosis after treatment. Clinical nursing pathway (CNP) refers to original nursing mode with good quality, outstanding efficiency, and low treatment spending. Few articles have reported the effect of CNP in patients with acute CH. The program is in urgent need of convinced evidence to prove the reliability. Thus, we perform this randomized controlled trial protocol and hypothesize that CNP is associated with improved outcomes and nursing satisfaction, reduced adverse reactions in patients with acute CH. METHOD: It is a single-center randomized controlled study to be conducted from October 2020 to October 2021. It was admitted via the Ethics Committee of the West China Hospital of Sichuan University (0038842/121). Eighty patients meet diagnostic standards for CH are included. The study group receives the clinical nursing path model. In the control group, patients receive the routine care before and after taking to the hospital. The main outcome contains the Barthel index score, the patient's degree of satisfaction about care, the length of hospital stay, and the risk of complications such as infection, bedsores and gastrointestinal function between the 2 groups. Six months after admission, the functional independence measure and Fugl Meyer score are recorded. All data are analyzed by the IBM SPSS Statistics, version 20 (IBM Corp., Armonk, NY edition). RESULTS: Table 1 shows the clinical outcomes between groups. CONCLUSION: CNP may improve the clinical outcomes for patients with acute CH and have a significant value in actual applications. TRIAL REGISTRATION NUMBER: researchregistry6061.


Assuntos
Hemorragia Cerebral/enfermagem , Procedimentos Clínicos , Satisfação do Paciente , Melhoria de Qualidade , Hemorragia Cerebral/psicologia , Hemorragia Cerebral/terapia , China , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto
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