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1.
Pediatr Res ; 2020 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-32225174

RESUMO

BACKGROUND: Autism spectrum disorder (ASD) is a neurodevelopmental disorder, and many individuals with ASD have gastrointestinal (GI) comorbidities. Vitamin A (VA) is an essential micronutrient that plays an important role in brain development and GI function. METHODS: A total of 323 children with ASD and 180 control children were enrolled in this study. Symptoms of ASD were assessed with the Child Autism Rating Scale (CARS), the Social Responsiveness Scale (SRS), and the Autism Behavior Checklist (ABC). Caregivers of the children completed questionnaires about GI symptoms. Serum retinol levels were detected with high-performance liquid chromatography (HPLC). RESULTS: Children with ASD and with GI comorbidity and constipation had considerably lower serum VA levels than autistic children without these symptoms. VA level was associated with CARS, SRS, and ABC scores, whereas GI symptoms were associated some SRS and ABC scores. The interaction of VAD and GI symptoms appeared to aggravate some of the core symptoms of children with ASD. CONCLUSIONS: VAD exacerbates core symptoms in children with ASD, and ASD children with GI comorbidities also have more serious core symptoms than ASD children without GI comorbidities. VAD comorbid with GI symptoms aggravates autistic children's core symptoms. IMPACT: VAD exacerbates core symptoms in children with ASD.ASD children with GI comorbidities have more serious core symptoms than ASD children without GI comorbidities.VAD comorbid with GI symptoms aggravates autistic children's core symptoms.We speculate that VAD might be related to a subtype of ASD that involves GI comorbidities.We believe that our findings will be of fundamental importance to the scientific community.

2.
Artigo em Inglês | MEDLINE | ID: mdl-32221789

RESUMO

PURPOSE: To investigate the potential development or metabolic risk in offspring derived from mice with transplanted frozen-thawed ovarian tissue. METHODS: Mice ovaries were intervened by vitrification (group V) and slow-freezing (group S) cryopreservation and orthotopic transplantation. Orthotopic transplantation of fresh ovarian (group F) and natural mating (group C) served as control groups. The fertility restoration and health conditions of generations were assessed by offspring counts, anti-fatigue and motor ability, and organ morphology. The methylation rate and expression level of imprinted genes (IGF2R, H19, SNRPN, and PLAGL1) were used to predict the potential risk of development in transplanted generations. RESULTS: Both the percentage of normal morphological follicles in different developmental periods and the litter size of receipt mice were comparable in all three transplanted groups. There was no significant difference in offspring mice's birth defects, body weight gain, anti-fatigue ability, or exercise capacity among the four groups. The methylation rate of IGF2R, H19, and PLAGL1 showed a significant variation in cryopreservation groups as compared with control groups, as well as a difference in gene expression. The SNRPN appeared to be stable in methylation status. There were no differences in mRNA expression in all groups. CONCLUSIONS: The different ovarian tissue cryopreservation methods did not influence either maternal fertility function or offspring growth. However, these technologies could affect the methylation rate and expression level of some development-related imprinting genes in the offspring, which may lead to some indeterminacy risk.

3.
J Proteome Res ; 2020 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-32182071

RESUMO

Pressure cycling technology (PCT)-assisted tissue lysis and digestion have facilitated reproducible and high-throughput proteomic studies of both fresh-frozen (FF) and formalin-fixed paraffin-embedded (FFPE) tissue of biopsy scale for biomarker discovery. Here, we present an improved PCT method accelerating the conventional procedures by about two-fold without sacrificing peptide yield, digestion efficiency, peptide, and protein identification. The time required for processing 16 tissue samples from tissues to peptides is reduced from about 6 to about 3 h. We analyzed peptides prepared from FFPE hepatocellular carcinoma (HCC) tissue samples by the accelerated PCT method using multiple MS acquisition methods, including short-gradient SWATH-MS, PulseDIA-MS, and 10-plex TMT-based shotgun MS. The data showed that up to 8541 protein groups could be reliably quantified from the thus prepared peptide samples. We applied the accelerated sample preparation method to 25 pairs (tumorous and matched benign) of HCC samples followed by a single-shot, 15 min gradient SWATH-MS analysis. An average of 18 453 peptides from 2822 proteins were quantified in at least 20% samples in this cohort, while 1817 proteins were quantified in at least 50% samples. The data not only identified the previously known dysregulated proteins such as MCM7, MAPRE1, and SSRP1 but also discovered promising novel protein markers, including DRAP1 and PRMT5. In summary, we present an accelerated PCT protocol that effectively doubles the throughput of PCT-assisted sample preparation of biopsy-level FF and FFPE samples without compromising protein digestion efficiency, peptide yield, and protein identification.

4.
Artigo em Inglês | MEDLINE | ID: mdl-32111589

RESUMO

The cyclodipeptide pulcherriminic acid produced by Bacillus licheniformis is derived from cyclo(L-Leu-L-Leu) and possesses excellent antibacterial activities. In this study, we achieved high-level production of pulcherriminic acid via multistep metabolic engineering of B. licheniformis DWc9n*. Firstly, we increased leucine (Leu) supply by overexpressing the ilvBHC-leuABCD operon and ilvD involved in Leu biosynthesis to obtain strain W1, and the engineered strain W2 was further attained by deletion of gene bkdAB encoding branched-chain α-keto acid dehydrogenase in W1. As a result, intracellular Leu content and pulcherriminic acid yield of W2 strain reached 147.4 mg/g DCW (dry cell weight) and 189.9 mg/L, which were 227.6% and 48.9% higher than those of DWc9n*, respectively. Secondly, the strain W3 was constructed through overexpressing leucyl-tRNA synthase gene leuS in W2, and it produced 367.7 mg/L pulcherriminic acid. Thirdly, the original promoter of pulcherriminic acid synthetase cluster yvmC-cypX in W3 was replaced with a proven strong promoter PbacA to attain the strain W4, and its pulcherriminic acid yield was increased to 507.4 mg/L. Finally, pulcherriminic acid secretion was strengthened via overexpressing the transporter gene yvmA in W4, and W4/pHY-yvmA obtained 556.1 mg/L pulcherriminic acid yield, increased by 337.8% compared to DWc9n*, which is currently the highest pulcherriminic acid yield to the best of our knowledge. Taken together, we provided an efficient strategy for enhancing pulcherriminic acid production, which could apply to high-level production of other cyclodipeptides.ImportancePulcherriminic acid is a cyclodipeptide derived from cyclo(L-Leu-L-Leu), which shares same iron chelation group with hydroxamate sidephores. Generally, pulcherriminic acid-producing strains could be perfect candidate for antibacterial and anti-plant pathogenic fungi agent. This study attained a promising pulcherriminic acid producing strain W4/pHY-yvmA via a multistep metabolic modification. The engineered strain W4/pHY-yvmA could be able to achieve 556.1 mg/L pulcherriminic acid production, which is the highest yield so far to the best of our knowledge.

5.
Nat Cell Biol ; 22(3): 353, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32066908

RESUMO

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

6.
World J Surg Oncol ; 18(1): 27, 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-32013993

RESUMO

BACKGROUND: The NCCN (National Comprehensive Cancer Network) Clinical Practice Guidelines in Oncology (NCCN guidelines) recommend radical resection for T1-2N0M0 patients with limited-stage small cell lung cancer (LS-SCLC). However, only about 5% of patients with small cell cancer (SCLC) were initially diagnosed as T1-2N0M0. The purpose of our study was to analyze and compare the effects of the comprehensive treatment including radical surgery and concurrent chemoradiotherapy on the prognosis of patients with LS-SCLC. METHODS: We comprehensively reviewed the medical data of patients with SCLC diagnosed by pathology in our hospital from January 2011 to April 2018. The Ethics Committee of West China Hospital of Sichuan University approved the study. Finally, 50 patients with good follow-up and complete medical data were selected as the surgical group (S group). According to the clinical characteristics of the patients in the S group, 102 LS-SCLC patients who received concurrent chemoradiotherapy in the same period were included in the CCRT group (concurrent chemoradiotherapy group) as the control group. Then according to the orders of the adjuvant treatments, the patients in the S group were divided into the SA group (radical surgery + adjuvant chemotherapy + adjuvant radiotherapy group, 30 cases in total) and the NS group (neoadjuvant chemotherapy + radical surgery + adjuvant chemotherapy ± adjuvant radiotherapy group, 20 cases in total) for subgroup analysis. The SPSS 23.0 software was used for statistical analysis, and the t test was used for group comparison; Kaplan-Meier was used for survival analysis. P < 0.05 demonstrates a statistically significant difference. RESULTS: The median progress-free survival (PFS) in the S group (73 months) was significantly better than that in the CCRT group (10.5 months, P < 0.0001), and the median overall survival (OS) in the S group (79 months) was also significantly better than that in the CCRT group (23 months, P < 0.0001). Subgroup analysis showed that there was no significant difference between the NS group and the SA group. CONCLUSIONS: For LS-SCLC patients, the comprehensive treatment including radical surgery (radical surgery + adjuvant chemotherapy ± adjuvant radiotherapy/neoadjuvant chemotherapy + radical surgery + adjuvant chemotherapy ± adjuvant radiotherapy)may be superior to concurrent chemoradiotherapy.

7.
Opt Lett ; 45(4): 828-831, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-32058481

RESUMO

Multiple light scattering in biomedical tissue limits the penetration depth of optical imaging systems such as optical coherence tomography. To increase the imaging depth in scattering media, a computational method based on coherent reflection matrix measurement has been developed using low coherence interferometry. The complex reflection matrix is obtained via point-by-point scanning followed by a phase-shifting method; then singular value decomposition is used to retrieve the singly back-scattered light. However, the in vivo application of the current reported method is limited due to the slow acquisition speed of the matrix. In this Letter, a wide-field heterodyne-detection method is adopted to speed up the complex matrix measurement at a deep tissue layer. Compared to the phase-shifting method, the heterodyne-detection scheme retrieves depth-resolved complex amplitudes faster and is more stable without mechanical movement of the reference mirror. As a result, the matrix measurement speed is increased by more than one order of magnitude.

8.
Protein Expr Purif ; 169: 105588, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32006655

RESUMO

The CRISPR-Cas13b system is a recently identified Class 2, RNA-targeting CRISPR-Cas system. The system has been repurposed to achieve robust mRNA knockdown and precise RNA-editing in mammalian cells. While the CRISPR-Cas13b system has become a powerful tool for nucleic acids manipulation, the mechanisms of the system are still not fully understood. Cas13b endonucleases from different bacterial species show poor overall sequence homologies, suggesting that structural (and probably functional) diversities may exist. It is therefore important to study CRISPR-Cas13b cases from different bacterial species. Here we report the expression, purification, and initial characterization of a Cas13b endonuclease that is associated with the 8th putative CRISPR locus from Porphyromonas gingivalis genome (Pgi8Cas13b). The full-length Pgi8Cas13b protein (1119 residues) was successfully expressed in E. Coli cells, and purified by affinity and ion-exchange chromatography methods. The purified protein is biologically active, being able to bind its cognate crRNA with high specificity and affinity. Preparation of biologically active Pgi8Cas13b protein provides the basis for further in vitro biochemical and biophysical studies of the Pgi8Cas13b CRISPR system.

9.
Nat Cell Biol ; 22(2): 200-212, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32015435

RESUMO

PIWI-interacting RNAs (piRNAs) are a class of small non-coding RNAs essential for fertility. In adult mouse testes, most piRNAs are derived from long single-stranded RNAs lacking annotated open reading frames (ORFs). The mechanisms underlying how piRNA sequences are defined during the cleavages of piRNA precursors remain elusive. Here, we show that 80S ribosomes translate the 5'-proximal short ORFs (uORFs) of piRNA precursors. The MOV10L1/Armitage RNA helicase then facilitates the translocation of ribosomes into the uORF downstream regions (UDRs). The ribosome-bound UDRs are targeted by piRNA processing machinery, with the processed ribosome-protected regions becoming piRNAs. The dual modes of interaction between ribosomes and piRNA precursors underlie the distinct piRNA biogenesis requirements at uORFs and UDRs. Ribosomes also mediate piRNA processing in roosters and green lizards, implying that this mechanism is evolutionarily conserved in amniotes. Our results uncover a function for ribosomes on non-coding regions of RNAs and reveal the mechanisms underlying how piRNAs are defined.

10.
J Infect Dis ; 2020 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-32067043

RESUMO

An ongoing outbreak of pneumonia associated with 2019 novel coronavirus (2019-nCoV) was reported in China. It is unclear if the infectivity exists during the incubation period, although a person-to-person transmission has been reported in previous studies. We report the epidemiological features of a familial cluster of four patients in Shanghai, of which one was 88 years old man with moving difficulties and was only exposed to his asymptomatic family members who developed symptoms later. The epidemiological evidence has shown a potential transmission of the 2019-nCoV during the incubation period.

11.
Thorac Cancer ; 11(3): 631-639, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31943824

RESUMO

BACKGROUND: This retrospective study compared the efficacy and side effect profile between postoperative adjuvant radiotherapy and chemoradiotherapy in stage II or stage III thoracic esophageal squamous cell carcinoma (TESCC) patients who underwent curative (R0) esophagectomy. METHODS: A total of 272 TESCC patients who underwent radical esophagectomy from 2007 to 2016 were included in this retrospective analysis. All cases were pathologically confirmed with stage II or III disease and 148 patients received postoperative chemoradiotherapy (CRT), while the remaining 124 patients received postoperative radiotherapy (RT) alone. RESULTS: In CRT and RT groups, the three-year overall survival rates were 51.3 versus 31.5% (P < 0.01) and the median overall survival (OS) was 39 months (95% CI, 31.6 to 46.3 months) and 30 months (95% CI, 21.0 to 38.9 months), respectively (P = 0.213). Three-year disease-free survival rates (DFS) were 30.5% versus 15.9% (P = 0.008), while the median DFS times were 26 months (95% CI, 17.7 to 34.3 months) and 19 months (95% CI, 16.4 to 21.6 months), respectively (P = 0.156). Univariate and multivariate analyses showed AJCC (American Joint Committee on Cancer seventh edition) stage and N stage were independent prognostic factors for overall survival, while the N stage was an independent prognostic factor for disease-free survival. CONCLUSIONS: Postoperative chemoradiotherapy led to one- and three-year overall survival benefits along with an obvious increase in treatment side effects for stage II to III TESCC patients, with no further improvement in five-year survival. However, the chemoradiotherapy benefits mainly favor stage III,number of resected lymph nodes less than 15, younger (less than 60 years old) and smoking patients.

12.
Female Pelvic Med Reconstr Surg ; 26(2): 155-158, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31990806

RESUMO

OBJECTIVE: Optical coherence tomography is a noninvasive technology that visualizes tissue microstructure with high spatial resolution. We designed a novel vaginal system that demonstrates a clear distinction between vaginal tissues planes. In this study, we sought to compare vaginal tomographic images of premenopausal, perimenopausal, and postmenopausal women, demonstrate feasibility of tracking vaginal tissue changes after treatment with fractional-pixel CO2 laser therapy, and obtain a histologic correlation of these findings. METHODS: Enrolled subjects underwent imaging and were divided into 3 groups based on menopausal status. Women with genitourinary syndrome of menopause who received fractional-pixel CO2 laser therapy were assessed before and after treatment. A cadaveric vagina was used to obtain tomographic and histologic images to assess for accuracy. Our primary outcome was mean vaginal epithelial thickness. Statistical analysis was performed using analysis of variance and t tests, respectively. RESULTS: Among 6 women, the mean vaginal epithelial thickness decreased with menopause (P < 0.01). Although change in epithelial thickness after fractional-pixel CO2 laser treatment varied between the 2 subjects evaluated, it increased significantly for the subject who reported improvement of vaginal symptoms (P < 0.01). Using a cadaveric specimen, optical biopsy was correlated to an hematoxylin and eosin-stained biopsy of the same vaginal site. CONCLUSIONS: This study establishes feasibility of optical coherence tomography in providing an optical biopsy of the vaginal epithelium and lamina propria. In addition, it demonstrates vaginal changes as women enter menopause. This report is the initial phase of a longitudinal cohort study to evaluate changes in vaginal microstructure after energy-based treatment.

13.
J Comp Eff Res ; 9(2): 93-102, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31958984

RESUMO

Aim: To assess the cost-effectiveness of crizotinib verses platinum-based doublet chemotherapy as the first-line treatment for anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer (NSCLC) in the real-world setting. Methods: Data from 163 advanced ALK positive NSCLC patients were collected from West China Hospital, Sichuan University (Chengdu, China). They were categorized into two groups as treated with crizotinib (n = 83) or chemotherapy (n = 80) as a first-line therapy. The progression-free survival (PFS) as the primary clinical outcome, and the direct medical costs were collected from hospital information systems. Incremental cost-effectiveness ratio (ICER) was calculated with costs, quality-adjusted life-years, as well as the costs discounted at 3% annually. Additionally, two different kinds of medical insurance (MI) for pharma-economic assessment were considered. Results: Crizotinib improved PFS versus chemotherapy in ALK positive patients (median PFS 19.67 m vs 5.47 m; p < 0.001). Moreover, crizotinib obtained an ICER of US$36,285.39 before the end of 2016, when crizotinib, pemetrexed and anti-angiogenesis drugs were not MI covered. This is more than the willingness to pay threshold (three-times of gross domestic product per capita in mainland China or Sichuan Province). However, ICER was US$7321.16, which is less than willingness to pay, when crizotinib and all chemotherapy drugs were covered by MI from the end of 2016. Sensitivity analysis demonstrated a 99.7% probability for crizotinib to be more cost-effective than chemotherapy, when crizotinib and all anticancer drugs were MI covered. One-way sensitivity analysis for the reimbursement ratio of crizotinib indicated that cost-effective tendency for crizotinib increased as reimbursement ratio increased. Conclusion: Crizotinib could be an effective, and cost-effective first-line treatment for ALK positive advanced NSCLC with the MI coverage currently available in Chengdu, Sichuan Province, China.

14.
Biochem Biophys Res Commun ; 524(1): 103-108, 2020 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-31980174

RESUMO

SP_0782 from Streptococcus pneumoniae is a dimeric PC4-like protein binding single-stranded DNA (ssDNA), and is potentially involved in maintenance of genome stability and natural transformation. SP_0782 binds with different lengths of ssDNA in various patterns through accommodating nucleotides differently in its two DNA-binding regions (DBRs). Here, we report the characterization of a novel site, leucine 20 (L20), which is not located in the DBRs but impairs the DNA binding when mutated to alanine (L20A). The L20A mutation markedly reduced the DNA-binding affinity of SP_0782 for ssDNA dT19G1, and affected the formation of high-order SP_0782:dT19G1 complexes. The side chain of L20 shows interactions with several residues at the backside of the DBRs in apo SP_0782 structure, and the L20A mutation led to a change of circular dichroism (CD) spectrum and broad chemical shift perturbations (CSPs) in NMR spectrum compared with the wild type. The most affected residues in NMR spectrum included F39 and R49 located in DBR2, as well as K60 in DBR1, which was suggested to be important for cooperative binding of ssDNA by the two subunits in SP_0782 dimer. Thus, the L20A mutation caused a local conformational change of SP_0782, which exerted an indirect effect on the DNA-binding interface and therefore impaired the affinity for ssDNA dT19G1. Interestingly, this L20 site is conserved in bacterial but not eukaryotic PC4-like proteins, suggesting an evolutionary divergence. This study provides an insight into the structure-function relationship of SP_0782, and an amino-acid site probably targeted for inhibiting bacteria selectively.

15.
Pestic Biochem Physiol ; 163: 164-174, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31973854

RESUMO

Helicoverpa armigera and H. assulta are two of the few insects that can feed on hot pepper fruits. Capsaicin and dihydrocapsaicin (i.e., capsaicinoids) are the principal pungent compounds in hot peppers. To explore possible molecular mechanisms of adaptation that allow these two species to consume capsaicinoids, the capacity of the three detoxification tissues (fat body, midgut, and Malpighian tubule) of the two pests, to metabolically degrade capsaicin and dihydrocapsaicin, was compared. The results showed that capsaicin and dihydrocapsaicin were metabolized by crude enzyme preparations from all three tissues of the two pests. Five metabolites of capsaicin, and five metabolites of dihydrocapsaicin were identified. Tissue and species differences in the degree of capsaicin and dihydrocapsaicin metabolism were observed. The specialist H. assulta had an overall greater capacity to degrade the capsaicinoids compared to the generalist H. armigera. Further, the midgut was the most significant contributor to capsaicinoid metabolism. The notably high specific activity in Malpighian tubules of H. armigera also further highlights the significance of this organ in xenobiotic detoxification. Alkyl hydroxylation and dehydrogenation were the main pathways for the oxidative biotransformation of both capsaicin and dihydrocapsaicin by cytochrome P450s. This study provides evidence that enhanced metabolic decomposition of capsaicinoids may be an adaptation explaining dietary preferences for Capsicum fruits by these two pests.


Assuntos
Capsicum , Mariposas , Animais , Sistema Enzimático do Citocromo P-450 , Frutas , Inativação Metabólica
16.
Nucleic Acids Res ; 48(1): 432-444, 2020 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-31713614

RESUMO

SP_0782 from Streptococcus pneumoniae is a dimeric protein that potentially binds with single-stranded DNA (ssDNA) in a manner similar to human PC4, the prototype of PC4-like proteins, which plays roles in transcription and maintenance of genome stability. In a previous NMR study, SP_0782 exhibited an ssDNA-binding property different from YdbC, a prokaryotic PC4-like protein from Lactococcus lactis, but the underlying mechanism remains unclear. Here, we show that although SP_0782 adopts an overall fold similar to those of PC4 and YdbC, the ssDNA length occupied by SP_0782 is shorter than those occupied by PC4 and YdbC. SP_0782 exhibits varied binding patterns for different lengths of ssDNA, and tends to form large complexes with ssDNA in a potential high-density binding manner. The structures of SP_0782 complexed with different ssDNAs reveal that the varied binding patterns are associated with distinct capture of nucleotides in two major DNA-binding regions of SP_0782. Moreover, a comparison of known structures of PC4-like proteins complexed with ssDNA reveals a divergence in the binding interface between prokaryotic and eukaryotic PC4-like proteins. This study provides insights into the ssDNA-binding mechanism of PC4-like proteins, and benefits further study regarding the biological function of SP_0782, probably in DNA protection and natural transformation.

17.
Reprod Toxicol ; 91: 109-115, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31759952

RESUMO

To explore possible associations between maternal use of micronutrient supplements and the subsequent vitamin levels and symptoms in offspring with autism spectrum disorder (ASD), a total of 416 children with ASD and 201 typically developing (TD) children were enrolled. The children born to mothers without folic acid (FA) and micronutrient supplementation during pregnancy had more severe social cognition impairments, social communication impairments, autism behaviour mannerisms, developmental delays in adaptive and gross motor behaviour and gastrointestinal problems than children born to mothers who used FA and micronutrient supplements (P<0.05). Interestingly, there was an association between maternal micronutrient supplementation and vitamin A (VA), vitamin D (VD) and folate levels in the ASD children (P<0.05), and levels of these vitamins also were associated with symptoms of ASD. Maternal FA and/or micronutrient supplementation may potentially moderate the symptoms of ASD. Interrupting the chain of micronutrient deficiencies between pregnant mothers and children may be beneficial in improving symptoms of ASD.

18.
Ann Vasc Surg ; 63: 325-331, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31626927

RESUMO

BACKGROUND: Carotid body tumor (CBT) is the most common head and neck paragangliomas. Surgical resection is the golden standard management for CBT. While preoperative embolization is still controversial, long-term outcomes and perioperative results are still deficient. We, here, presented the outcomes of surgical treatment for CBT without preoperative embolization at our institution. METHODS: In this retrospective study, we collected data from 101 patients who received surgical treatment for CBTs without preoperative embolization from 2011 to 2016. In addition, we attempted to conduct 2 years of follow-up under the guidance of both neurologist and vascular surgeon. Patients' demographics, clinical characteristics, complications, and follow-up results were all analyzed with descriptive statistics. RESULTS: Complete resection of the CBT was achieved in 101 cases (100%). Postoperative adverse events (AEs) mostly observed during hospitalization were as follows: tongue bias (I: 4, 36.4%; II: 8, 19.5%; III: 13, 26.5%), hoarseness (I: 1, 9.1%; II: 4, 9.8%; III: 7, 14.3%), dysphagia (I: 0; II: 2, 4.9%; III: 7, 14.3%), and hematoma (I: 0; II: 0; III: 1, 2.0%). No other serious AEs were observed. The total incidence of AEs in type I patients was 5 (45.5%), 14 (34.1%) in type II, and 28 (57.1%) in type III, and the type III group has significantly higher than the other two groups. At the end of 2 years of follow-up, there were no AEs in type I patients. The number of patients with AEs in type III was greater than that in type II, although there was no significant difference. Based on our findings, 3 most commonly injured cranial nerves (CNs) after surgical resection of CBT were CN XII (hypoglossal nerve, 21.9%), CN X (vagus nerve, 20.3%), and recurrent laryngeal nerve (18.8%). CONCLUSIONS: Surgical management without preoperative embolization for CBT patients is a safe and effective therapeutic approach.

19.
Artigo em Inglês | MEDLINE | ID: mdl-31785320

RESUMO

BACKGROUND: Obsessive-compulsive disorder (OCD) is a clinically heterogeneous condition. To better understand and treat patients, symptomatology of OCD has been categorized into more homogenous symptom dimensions. The autogenous-reactive classification model has proven helpful in the elucidation of the neurobiological substrates for clinical heterogeneity in OCD. The purpose of the current study was to systematically compare regional and network functional alterations between OCD subtypes based on the autogenous-reactive model. METHODS: Autogenous-type OCD patients (OCD-AO, n = 40), reactive-type patients (OCD-RO, n = 42), and healthy controls (HC, n = 70) underwent functional magnetic resonance imaging (fMRI) scans. The amplitude of low-frequency fluctuation (ALFF) and regional homogeneity (ReHo) were compared among subjects. Areas of abnormal local spontaneous brain activity that differentiated OCD-AO and OCD-RO patients were identified and entered as seeds in functional connectivity (FC) analysis. RESULTS: Compared to OCD-RO patients and HC participants, OCD-AO patients showed increased ALFF in the left anterior insula (AI), increased ReHo in the right AI, and hyperconnectivity between bilateral AI and anterior cingulate cortex (ACC). Both OCD-AO and OCD-RO patients shared regional function deficits in several areas within the prefrontal cortex, and stronger FC between bilateral AI and major nodes of the default mode network (DMN) compared to healthy controls. CONCLUSION: The current results suggest that aberrant functional interaction between the salience network (SN) and the DMN may represent a common substrate in the pathophysiology of OCD, while impaired functional coupling within the SN is distinct to autogenous-type OCD patients. These findings provide further neurobiological evidence to support the autogenous-reactive classification model and contribute to the understanding of the neurobiological basis for clinical heterogeneity in OCD.

20.
Nucleic Acids Res ; 48(D1): D1031-D1041, 2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31691823

RESUMO

Knowledge of therapeutic targets and early drug candidates is useful for improved drug discovery. In particular, information about target regulators and the patented therapeutic agents facilitates research regarding druggability, systems pharmacology, new trends, molecular landscapes, and the development of drug discovery tools. To complement other databases, we constructed the Therapeutic Target Database (TTD) with expanded information about (i) target-regulating microRNAs and transcription factors, (ii) target-interacting proteins, and (iii) patented agents and their targets (structures and experimental activity values if available), which can be conveniently retrieved and is further enriched with regulatory mechanisms or biochemical classes. We also updated the TTD with the recently released International Classification of Diseases ICD-11 codes and additional sets of successful, clinical trial, and literature-reported targets that emerged since the last update. TTD is accessible at http://bidd.nus.edu.sg/group/ttd/ttd.asp. In case of possible web connectivity issues, two mirror sites of TTD are also constructed (http://db.idrblab.org/ttd/ and http://db.idrblab.net/ttd/).

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