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2.
J Gen Intern Med ; 2021 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-33948795

RESUMO

BACKGROUND: Frailty is often cited as a factor influencing oral anticoagulation (OAC) prescription in patients with non-valvular atrial fibrillation (NVAF). We sought to determine the prevalence of frailty and its association with OAC prescription in older veterans with NVAF. METHODS: We used ICD-9 codes in Veterans Affairs (VA) records and Medicare claims data to identify patients with NVAF and CHA2DS2VASC ≥2 receiving care between February 2010 and September 2015. We examined rates of OAC prescription, further stratified by direct oral anticoagulant (DOAC) or vitamin K antagonist (VKA). Participants were characterized into 3 categories: non-frail, pre-frail, and frail based on a validated 30-item EHR-derived frailty index. We examined relations between frailty and OAC receipt; and frailty and type of OAC prescribed in regression models adjusted for factors related to OAC prescription. RESULTS: Of 308,664 veterans with NVAF and a CHA2DS2VASC score ≥2, 121,839 (39%) were prescribed OAC (73% VKA). The mean age was 77.7 (9.6) years; CHA2DS2VASC and ATRIA scores were 4.6 (1.6) and 5.0 (2.9) respectively. Approximately a third (38%) were frail, another third (32%) were pre-frail, and the remainder were not frail. Veterans prescribed OAC were younger, had higher bleeding risk, and were less likely to be frail than participants not receiving OAC (all p's<0.001). After adjustment for factors associated with OAC use, pre-frail (OR: 0.89, 95% CI: 0.87-0.91) and frail (OR: 0.66, 95% CI: 0.64-0.68) veterans were significantly less likely to be prescribed OAC than non-frail veterans. Of those prescribed OAC, pre-frail (OR:1.27, 95% CI: 1.22-1.31) and frail (OR: 1.75, 95% CI: 1.67-1.83) veterans were significantly more likely than non-frail veterans to be prescribed a DOAC than a VKA. CONCLUSIONS: There are high rates of frailty among older veterans with NVAF. Frailty using an EHR-derived index is associated with decreased OAC prescription.

3.
Mol Plant Pathol ; 2021 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-33951267

RESUMO

In this study, we used virus-mediated gene silencing technology and found that the HSP17.4 gene-silenced cultivar Sweet Charlie plants were more susceptible to Colletotrichum gloeosporioides than the wild-type Sweet Charlie, and the level of infection was even higher than that of the susceptible cultivar Benihopp. The results of differential quantitative proteomics showed that after infection with the pathogen, the expression of the downstream response genes NPR1, TGA, and PR-1 of the salicylic acid (SA) signalling pathway was fully up-regulated in the wild-type Sweet Charlie, and the expression of the core transcription factor MYC2 of the jasmonic acid (JA) pathway was significantly down-regulated. The expression of the proteins encoded by these genes did not change significantly in the HSP17.4-silenced Sweet Charlie, indicating that the expression of HSP17.4 activated the up-regulation of downstream signals of SA and inhibited the JA signal pathway. The experiments that used SA, methyl jasmonate, and their inhibitors to treat plants provide additional evidence that the antagonism between SA and JA regulates the resistance of strawberry plants to C. gloeosporioides.

4.
Gene ; : 145692, 2021 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-33961972

RESUMO

Several evolutionarily conserved classes of transcriptional regulators were involved in diverse sex determination and differentiation pathways across taxa, whereas their roles in most mollusks is still limited. The Pacific oyster Crassostrea gigas, a dioecious bivalve with sex reversal, could be an ideal model for this issue because of its complex sexuality and potential disruption of sex differentiation in triploid individuals. Here, two mRNA splicing isoforms of a DM domain gene CgDsx and two isoforms of a novel sex-related CgBHMG1 (ortholog of BHMG1 in mammals) were identified in C. gigas. Real time PCR showed that two isoforms of CgDsx and one isoform of CgBHMG1 displayed male-specific expression in diploid oysters, opposite with the female-specific CgFoxl2 (a potential factor of female gonadic differentiation). Interestingly, the four sex-specific transcripts in diploid oyster were expressed in triploid oysters with opposite sex, triploid hermaphrodites and individuals at stage I that sex could not be determined. Subsequent in situ hybridization analysis on gonads of diploid oysters revealed predominant expression of CgDsx in spermatogonia of testes, CgBHMG1 in spermatocytes of testes and follicle cells of ovaries, and CgFoxl2 in follicle cells of ovaries and some male germ cells in testes. And aberrant co-expression of the three genes in triploid oysters was localized in gonadal tubules of gonads at stage I, ovarian follicle cells and undetermined gonial cells in nontypical hermaphroditic gonads with rare female materials. From the above, temporal and spatial expression of sex-related genes in diploid and triploid gonads indicated that CgDsx and CgFoxl2 might mainly function in C. gigas sex differentiation, and CgBHMG1 appeared as a factor involved in meiosis. This work will help to illuminate the gene network of sex differentiation in bivalves and provides new sight on this issue from comparison between diploid and triploid individuals.

5.
Int J Surg Case Rep ; 82: 105785, 2021 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-33865196

RESUMO

INTRODUCTION: Bladder urothelial carcinoma rarely spreads to the gastrointestinal tract, and its presentation in the rectum varies. We report a case of a patient who presented with an annular constriction of the rectum. PRESENTATION OF CASE: A 60-year-old man was referred to our hospital with chief complaints of anal stricture and partial obstruction for about 1 month. Computed tomography and magnetic resonance imaging revealed diffuse wall thickening of the rectum, possible high cellularity in the lower portion of urinary bladder, and lesions in the visible pelvic bony structure. A colonoscopy showed a contiguous annular constriction from 5 to 15 cm above the anal verge. Carcinoembryonic antigen and carbohydrate antigen 19-9 levels were 39.75 ng/mL and 139.2 U/mL, respectively. A transurethral bladder biopsy revealed high-grade urothelial cell carcinoma, and anal biopsy showed a poorly differentiated carcinoma arranged in a small nested pattern within the subepithelial area of the anorectal tissue. A colostomy was performed, and the patient was transferred to another hospital for further treatment after series of survey with lung metastasis. DISCUSSION: Invasive bladder cancers rarely infiltrates into the rectum and is known with the difficulty diagnosis by colonoscopy. Furthermore, the secondary rectum tumor due to bladder cancer had poor record for survival in the literature review. CONCLUSION: This case of bladder urothelial carcinoma penetrating to the rectum was interesting because it mimicked proctitis with diffuse annular swelling observed in the colonoscopy.

6.
Int J Mol Sci ; 22(9)2021 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-33922596

RESUMO

As G protein coupled receptors, sphingosine-1-phosphate receptors (S1PRs) have recently gained attention for their role in modulating inflammatory bone loss diseases. Notably, in murine studies inhibiting S1PR2 by its specific inhibitor, JTE013, alleviated osteoporosis induced by RANKL and attenuated periodontal alveolar bone loss induced by oral bacterial inflammation. Treatment with a multiple S1PRs modulator, FTY720, also suppressed ovariectomy-induced osteoporosis, collagen or adjuvant-induced arthritis, and apical periodontitis in mice. However, most previous studies and reviews have focused mainly on how S1PRs manipulate S1P signaling pathways, subsequently affecting various diseases. In this review, we summarize the underlying mechanisms associated with JTE013 and FTY720 in modulating inflammatory cytokine release, cell chemotaxis, and osteoclastogenesis, subsequently influencing inflammatory bone loss diseases. Studies from our group and from other labs indicate that S1PRs not only control S1P signaling, they also regulate signaling pathways induced by other stimuli, including bacteria, lipopolysaccharide (LPS), bile acid, receptor activator of nuclear factor κB ligand (RANKL), IL-6, and vitamin D. JTE013 and FTY720 alleviate inflammatory bone loss by decreasing the production of inflammatory cytokines and chemokines, reducing chemotaxis of inflammatory cells from blood circulation to bone and soft tissues, and suppressing RANKL-induced osteoclast formation.

7.
Biomed Res Int ; 2021: 6669792, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33880376

RESUMO

Although several studies have reported the multiple systemic effects of betel nut (BN) chewing, analyses performed on the colonic system have been few. To analyze the association between BN chewing and diverticulosis, we conducted a cross-sectional study of 5,586 eligible participants who underwent colonoscopy at a medical center in Taiwan from 2010 to 2016. BN chewing was recorded based on an assessment of personal history. Diverticulosis was categorized based on whether colonoscopies had been performed during health examinations by trained physicians at Tri-Service General Hospital. The association between different exposures, including cigarette, alcohol, BN, and diverticulosis, was also analyzed. Our study included 3,161 males and 2,425 females, and males have significantly higher prevalence rates of BN chewing than females (11.1% versus 0.3%, respectively). In the male group, BN chewing had an adjusted odd ratio (OR): 1.65(95% confident interval (CI): 1.12-2.44) with the presence of diverticulosis. Among the combination of exposures of cigarette, alcohol, and BN, the group with BN chewing combined with smoking and drinking showed significant association between diverticulosis with adjusted OR: 1.909 (95% CI, 1.188-3.065). Further subgroup analysis displayed adjusted OR: 2.310 (95% CI, 1.245-4.287) in obesity and OR: 2.406 (95% CI, 1.205-4.803) in elderly male. Thus, BN chewing is independently associated with diverticulosis in male.

8.
Huan Jing Ke Xue ; 42(5): 2133-2142, 2021 May 08.
Artigo em Chinês | MEDLINE | ID: mdl-33884782

RESUMO

Atmospheric particle number size distributions were measured by a wide-range particle size spectrometer and a scanning mobility particle size spectrometer in the summertime and wintertime in the coastal area of Qingdao (China). The inorganic and organic gaseous precursors and particulate chemical composition were measured to characterize new particle formation (NPF) events by combining meteorological parameters and backward trajectories. In summer, the occurrence frequency of NPF events was 18% lower. However, the atmospheric particle number concentration increased by approximately 1-4 times during the NPF events compared with those without NPF. The apparent formation rates and growth rates were (5.2±4.3) cm-3·s-1 and (6.5±2.2) nm·h-1, respectively, except for a special NPF event on July 20. The correlation analysis results implied that biogenic volatile organic compounds (BVOCs) seemingly favor NPF, and the reverse is true for anthropogenic volatile organic compounds (AVOCs). The occurrence frequency of NPF events of 27% in winter was clearly higher than that in summer. The apparent formation rates and growth rates, i.e., (3.3±3.1) cm-3·s-1 and (5.3±3.3) nm·h-1, decreased, although the decreases were not significant (P>0.05). The correlation analyses implied that AVOCs favored NPF. However, BVOCs had no correlation with NPF. For the cases in which new particles could grow to CCN sizes (>50 nm), the particle growth characteristics showed significant seasonal differences, i.e., in summer, new particles could grow to CCN sizes via photochemical reactions, whereas in winter, second-stage growth driven by the formation of nitrate aerosols was needed to grow new particles to CCN sizes.

9.
Aging (Albany NY) ; 13(7): 9900-9910, 2021 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-33882027

RESUMO

Long non-coding RNA (LncRNA) MNX1 antisense RNA 1(MNX1-AS1) is associated with the pathology of numerous cancers. But, the role and underlying pathways of MNX1-AS1 in the regulation of laryngeal squamous cell carcinoma (LSCC) is not known. We demonstrated remarkably elevated levels of MNX1-AS1 in the LSCC tissues, which was correlated with poor disease prognosis. Moreover, MNX1-AS1-silencing strongly suppressed LSCC cell proliferation, migration, and invasion. We also demonstrated that MNX1-AS1 sequesters that activity of miR-370, thereby releasing Forkhead Box ml (FoxM1) from the inhibitory actions of MNX1-AS1. Furthermore, the positive correlation of MNX1-AS1 and FoxM1 as well as the converse correlation between miR-370 and MNX1-AS1 (or FoxM1) were revealed in LSCC tissues using experiments. Based on rescue assays, FoxM1 overexpression or miR-370 downregulation partially recovered the inhibitory effect of MNX1-AS1 silencing on LSCC cells. Moreover, knockdown of MNX1-AS1 retarded tumor growth in nude mice model. In summary, these findings verified that MNX1-AS1 modulated LSCC progression by competitively binding with miR-370 to regulate FoxM1.

10.
Adv Nutr ; 2021 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-33903896

RESUMO

Emerging evidence shows an association between protein intake during infancy and later obesity risk, and that association may differ by protein sources. This systematic review summarized and evaluated prospective cohort studies assessing the long-term association of total protein intake and protein sources during infancy (from birth to 2 y) with subsequent obesity outcomes in childhood or adolescence. Literature searches were conducted in Embase, Medline, Scopus, and Web of Science. Sixteen studies that reported associations between total protein intake and/or protein intake from different sources from birth to 2 y and ≥1 obesity outcomes in childhood or adolescence from 9 cohorts were identified. Most studies (11/16) were rated as high quality. The most frequently reported association was total protein intake and BMI (up to 10 y) with 6 out of 7 cohorts showing significant positive associations. Similar associations were found for animal protein, but not for plant protein. Limited studies examined the association between protein intake (both total and sources) and body composition (body fat, fat mass, and fat-free mass) and revealed inconsistent findings. Overall, higher intakes of total and animal protein during infancy were associated with higher BMI in childhood and adolescence. Future studies investigating the contribution of protein sources in long-term obesity development are needed. This review was registered at PROSPERO as CRD42020166540.

11.
Artigo em Inglês | MEDLINE | ID: mdl-33905241

RESUMO

Flexible electronics has recently captured extensive attention due to its intriguing functionalities and great potential for influencing our daily life. In addition, with the increasing demand for green energy, photoelectrochemical (PEC) water splitting is a clean process that directly converts solar energy to chemical energy in the form of hydrogen. Thus the development of flexible green energy electronics represents a new domain in the research field of energy harvesting. In this work, we demonstrate the BiVO4 (BVO)/WO3/ITO/muscovite heterostructure photoelectrode for water splitting with flexible characteristics. The performance of BVO was modified by specific crystal facets, and the BVO/WO3 bilayer exhibited superior performance of 33% enhanced PEC activity at 1 V vs Ag/AgCl compared with pure BVO due to the proper staggered band alignment. Moreover, excellent mechanical stability was verified by a series of bending modes. This study demonstrates a pathway to a flexible photoelectrode for developing innovative devices for solar fuel generation.

12.
Can J Gastroenterol Hepatol ; 2021: 6677821, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33791254

RESUMO

Purpose. To compare the diagnostic value of texture analysis- (TA-) derived parameters from out-of-phase T1W, in-phase T1W, and T2W images in the classification of the early stage of liver fibrosis. Methods. Patients clinically diagnosed with hepatitis B infection, who underwent liver biopsy and noncontrast MRI scans, were enrolled. TA parameters were extracted from out-of-phase T1-weighted (T1W), in-phase T1W, and T2-weighted (T2W) images and calculated using Artificial Intelligent Kit (AK). Features were extracted including first-order, shape, gray-level cooccurrence matrix, gray-level run-length matrix, neighboring gray one tone difference matrix, and gray-level differential matrix. After statistical analyses, final diagnostic models were constructed. Receiver operating curves (ROCs) and areas under the ROC (AUCs) were used to assess the diagnostic value of each final model and 100-time repeated cross-validation was applied to assess the stability of the logistic regression models. Results. A total of 57 patients were enrolled in this study, with 27 in the fibrosis stage < 2 and 30 in stages ≥ 2. Overall, 851 features were extracted per ROI. Eight features with high correlation were selected by the maximum relevance method in each sequence, and all had a good diagnostic performance. ROC analysis of the final models showed that all sequences had a preferable performance with AUCs of 0.87, 0.90, and 0.96 in T2W and in-phase and out-of-phase T1W, respectively. Cross-validation results reported the following values of mean accuracy, specificity, and sensitivity: 0.98 each for out-of-phase T1W; 0.90, 0.89, and 0.90 for in-phase T1W; and 0.86, 0.88, 0.84 for T2W in the training set, and 0.76, 0.81, and 0.72 for out-of-phase T1W; 0.74, 0.72, and 0.75 for in-phase T1W; and 0.63, 0.64, and 0.63 for T2W for the test group, respectively. Conclusion. Noncontrast MRI scans with texture analysis are viable for classifying the early stages of liver fibrosis, exhibiting excellent diagnostic performance.

13.
Zhen Ci Yan Jiu ; 46(3): 194-200, 2021 Mar 25.
Artigo em Chinês | MEDLINE | ID: mdl-33798291

RESUMO

OBJECTIVE: To explore the effect of moxibustion at "Zusanli"(ST36) and "Shenshu"(BL23) on synovitis, and expressions of miR-155, Toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), interlukine(IL-1) receptor-associated kinase (IRAK1), tumor necrosis factor receptor-associated factor 6 (TRAF6), nuclear factor κB (NF-κB), IL-1ß, tumor necrosis factor receptor (TNF)-α and IL-6 mRNA and protein of synovial membrane in rheumatoid arthritis (RA) rats, so as to explore its mechanism underlying improvement of RA. METHODS: A total of 48 male Wistar rats were randomly divided into normal control, model, moxibustion and antagonist groups (n=12 rats in each group). The RA model was replicated by placing the rats in a wind, cold and wet environment and injection of Freund's complete adjuvant (CFA, 0.5 mL) into the right hindlimb foot plantar. Moxibustion was applied to bilateral ST36 and BL23 for 30 min, once daily for 21 consecutive days. Rats of the antagonist group was treated by injection of TLR4 antagonist (TAK-242, 1 mg/mL, 0.1 mg/kg) via tail vein, once per day for consecutive 21 d. The joint swelling degree (JSD) and arthritis index (AI, red swelling scale) were determined, and the expression levels of various indicators of miR-155, and TLR4, myeloid MyD88, IRAK1, TRAF6, NF-κB, IL-1ß, TNF-α and IL-6 mRNA and protein were assayed by quantitative real time-PCR and Western blot, separately. RESULTS: Compared with the normal control group, the JSD and AI, and the expression levels of synovial miR-155, TLR4, MyD88, IRAK1, TRAF6, NF-κB, IL-1ß, TNF-α and IL-6 mRNA and protein were significantly increased in the model group (P<0.01). Compared with the model group, the increased levels of JSD and AI, and the expression levels of synovial miR-155, TLR4, MyD88, IRAK1, TRAF6, NF-κB, IL-1ß, TNF-α and IL-6 mRNA and protein were notably down-regulated in both moxibustion and antagonist groups (P<0.01). The effects of moxibustion were evidently superior to the antagonist in down-regulating the abovementioned indexes (P<0.01), except TLR4 mRNA and protein. CONCLUSION: Moxibustion at ST36 and BL23 can reduce the synovitis of RA rats, which is related to its effects in suppressing the expressions of miR-155, TLR4, MyD88, IRAK1, TRAF6, NF-κB, IL-1ß, TNF-α and IL-6 mRNA and protein (i.e., inhibition of miR-155/TLR4/NF-κB signaling).


Assuntos
Artrite Reumatoide , MicroRNAs , Moxibustão , Sinovite , Animais , Artrite Reumatoide/genética , Artrite Reumatoide/terapia , Masculino , MicroRNAs/genética , NF-kappa B/genética , Ratos , Ratos Wistar , Receptor 4 Toll-Like/genética
14.
Front Cell Infect Microbiol ; 11: 650163, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33816355

RESUMO

Background: The prompt diagnosis of pulmonary tuberculosis (PTB) remains a challenge in clinical practice. The present study aimed to optimize an algorithm for rapid diagnosis of PTB in a real-world setting. Methods: 28,171 adult inpatients suspected of having PTB in China were retrospectively analyzed. Bronchoalveolar lavage fluid (BALF) and/or sputum were used for acid-fast bacilli (AFB) smear, Xpert MTB/RIF (Xpert), and culture. A positive mycobacterial culture was used as the reference standard. Peripheral blood mononuclear cells (PBMC) were used for T-SPOT.TB. We analyzed specimen types' effect on these assays' performance, determined the number of smears for diagnosing PTB, and evaluated the ability of these assays performed alone, or in combination, to diagnose PTB and nontuberculous mycobacteria (NTM) infections. Results: Sputum and BALF showed moderate to substantial consistency when they were used for AFB smear or Xpert, with a higher positive detection rate by BALF. 3-4 smears had a higher sensitivity than 1-2 smears. Moreover, simultaneous combination of AFB and Xpert correctly identified 44/51 of AFB+/Xpert+ and 6/7 of AFB+/Xpert- cases as PTB and NTM, respectively. Lastly, when combined with AFB/Xpert sequentially, T-SPOT showed limited roles in patients that were either AFB+ or Xpert+. However, T-SPOTMDC (manufacturer-defined cut-off) showed a high negative predicative value (99.1%) and suboptimal sensitivity (74.4%), and TBAg/PHA (ratio of Mycobacterium tuberculosis-specific antigens to phytohaemagglutinin spot-forming cells, which is a modified method calculating T-SPOT.TB assay results) ≥0.3 demonstrated a high specificity (95.7%) and a relatively low sensitivity (16.3%) in AFB-/Xpert- patients. Conclusions: Concurrently performing AFB smear (at least 3 smears) and Xpert on sputum and/or BALF could aid in rapid diagnosis of PTB and NTM infections in a real-world high-burden setting. If available, BALF is preferred for both AFB smear and Xpert. Expanding this algorithm, PBMC T-SPOTMDC and TBAg/PHA ratios have a supplementary role for PTB diagnosis in AFB-/Xpert- patients (moderately ruling out PTB and ruling in PTB, respectively). Our findings may also inform policy makers' decisions regarding prevention and control of TB in a high burden setting.

15.
Artigo em Inglês | MEDLINE | ID: mdl-33846561

RESUMO

Diffuse alveolar haemorrhage (DAH) is a life-threatening pulmonary complication occurring after allogeneic haematopoietic stem cell transplantation (allo-HSCT) without an explicit aetiology or a standard treatment. This study aimed to explore the occurrence and prognosis of DAH after allo-HSCT, in addition to comparing discrepancies in the incidence, clinical characteristics and outcomes of DAH between patients undergoing haploidentical HSCT (HID-HSCT) and matched related donor HSCT (MRD-HSCT). We retrospectively evaluated 92 consecutive patients among 3987 patients with a confirmed diagnosis of DAH following allo-HSCT (HID: 71 patients, MRD: 21 patients). The incidence of DAH after allo-HSCT was 2.3%, 2.4% after HID-HSCT and 2.0% after MRD-HSCT (P = 0.501). The prognosis of patients with DAH after transplantation is extremely poor. The duration of DAH was 7.5 days (range, 1-48 days). The probabilities of overall survival (OS) were significantly different between patients with and without DAH within 2 years after transplantation (P < 0.001). According to the Cox regression analysis, a significant independent risk factor for the occurrence of DAH was delayed platelet engraftment (P < 0.001), and a high D-dimer level (>500 ng/ml) was a significant risk factor for the poor prognosis of DAH. HID-HSCT is similar to MRD-HSCT in terms of the outcomes of DAH.

16.
Artigo em Inglês | MEDLINE | ID: mdl-33851818

RESUMO

Single crystal wafers, such as silicon, are the fundamental carriers of advanced electronic devices. However, these wafers exhibit rigidity without mechanical flexibility, limiting their applications in flexible electronics. Here, we propose a new approach to fabricate 1.5 in. flexible functional zinc oxide (ZnO) single crystal wafers with high electron mobility (>100 cm2 V-1 s-1) and optical transparency (>80%) by a combination of thin-film deposition, a chemical solution method, and surficial treatment. The uniformity of the flexible single crystal wafers is examined by an advanced scanning X-ray diffraction technique and photoluminescence spectroscopy. The transport properties of ZnO flexible single crystal wafers retain their pristine states under various bending conditions, including cyclability and endurability. This approach demonstrates a breakthrough in the fabrication of the flexible single crystal wafers for future flexible optoelectronic applications.

17.
Oncologist ; 2021 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-33844372

RESUMO

BACKGROUND: The impact of HER2 somatic mutations in colorectal carcinoma (CRC) has not been well studied and its relationship with microsatellite instability-high (MSI-H) is yet to be fully elucidated. MATERIALS AND METHODS: From February 2017 to February 2020, the data of patients with CRC who underwent next-generation sequencing and had detailed record of clinicopathological information were investigated. HER2 alteration and its relationship with MSI-H were analyzed. RESULTS: Among 731 patients who underwent sequencing, 55 patients (7.5%) had HER2 alteration, including 29 (4.0%) with HER2 somatic mutations, 24 (3.3%) with HER2 gene amplification, and 2 patients (0.2%) with both HER2 mutations and amplification. R678Q was the most common mutated kinase domain, and no HER2 kinase domain in-frame insertions/deletions were found in HER2 mutated cases. MSI-H was found in 5.2% of our cohort and 36.8% of MSI-H patients had HER2 mutation. For HER2 mutated cases, 48.3% were MSI-H, whereas none of the HER2 amplification cases were MSI-H. MSI-H patients with HER2 mutation had significantly worse median progression-free survival for programmed death-1 (PD-1) antibody than those without HER2 alteration (p = .036). CONCLUSION: High MSI-H rate was found in HER2 mutated cases, but no MSI-H was found in HER2 amplification cases. MSI-H patients with HER2 mutated had worse progression-free survival for PD-1 antibody than those without. IMPLICATIONS FOR PRACTICE: This study highlights the high microsatellite instability-high (MSI-H) rate in HER2 mutated cases but no MSI-H in HER2 amplification cases. Moreover MSI-H patients with HER2 mutated had worse progression-free survival for programmed death-1 antibody than those without. Further research to explore the internal relationship between HER2 alteration and MSI-H is needed.

18.
Sci Rep ; 11(1): 8412, 2021 04 16.
Artigo em Inglês | MEDLINE | ID: mdl-33863958

RESUMO

A reasonable prediction of infectious diseases' transmission process under different disease control strategies is an important reference point for policy makers. Here we established a dynamic transmission model via Python and realized comprehensive regulation of disease control measures. We classified government interventions into three categories and introduced three parameters as descriptions for the key points in disease control, these being intraregional growth rate, interregional communication rate, and detection rate of infectors. Our simulation predicts the infection by COVID-19 in the UK would be out of control in 73 days without any interventions; at the same time, herd immunity acquisition will begin from the epicentre. After we introduced government interventions, a single intervention is effective in disease control but at huge expense, while combined interventions would be more efficient, among which, enhancing detection number is crucial in the control strategy for COVID-19. In addition, we calculated requirements for the most effective vaccination strategy based on infection numbers in a real situation. Our model was programmed with iterative algorithms, and visualized via cellular automata; it can be applied to similar epidemics in other regions if the basic parameters are inputted, and is able to synthetically mimic the effect of multiple factors in infectious disease control.


Assuntos
/diagnóstico , Modelos Teóricos , /epidemiologia , /virologia , Humanos , Prognóstico , Reino Unido/epidemiologia , Vacinação/psicologia
19.
Cell Stem Cell ; 2021 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-33887179

RESUMO

The hypothalamus contains an astounding heterogeneity of neurons that regulate endocrine, autonomic, and behavioral functions. However, its molecular developmental trajectory and origin of neuronal diversity remain unclear. Here, we profile the transcriptome of 43,261 cells derived from Rax+ hypothalamic neuroepithelium to map the developmental landscape of the mouse hypothalamus and trajectory of radial glial cells (RGCs), intermediate progenitor cells (IPCs), nascent neurons, and peptidergic neurons. We show that RGCs adopt a conserved strategy for multipotential differentiation but generate Ascl1+ and Neurog2+ IPCs. Ascl1+ IPCs differ from their telencephalic counterpart by displaying fate bifurcation, and postmitotic nascent neurons resolve into multiple peptidergic neuronal subtypes. Clonal analysis further demonstrates that single RGCs can produce multiple neuronal subtypes. Our study reveals that multiple cell types along the lineage hierarchy contribute to fate diversification of hypothalamic neurons in a stepwise fashion, suggesting a cascade diversification model that deconstructs the origin of neuronal diversity.

20.
Huan Jing Ke Xue ; 42(5): 2440-2448, 2021 May 08.
Artigo em Chinês | MEDLINE | ID: mdl-33884815

RESUMO

Paddy soil often undergoes frequent dry-wet alternation. The change in water status not only affects the physical and chemical properties of the soil, but also changes the structure and diversity of the soil microbial communities, which in turn determines the rate of soil organic carbon mineralization. However, the effects of different water conditions and soil microbial biomass levels on the process of soil organic carbon mineralization and its mechanisms are still unclear. Therefore, this study took typical subtropical paddy soil as the research object, applied a laboratory incubation experiment with two water treatments of dry-wet and continuous flooding, and reduced the soil microbial biomass through chloroform fumigation, thereby obtaining high and low soil microbial biomass carbon contents, to elucidate the influencing mechanisms of microbial biomass and water conditions on organic carbon mineralization in paddy soil. The results showed that during the first 30 d of incubation, the dry-wet treatment was in a non-flooded stage and its cumulative CO2 emissions were significantly lower than those of the continuous flooded treatment. After 30 d, the dry-wet treatment entered the flooded stage. The difference in the cumulative CO2 emissions of the soils with a high microbial biomass carbon content between the dry-wet and continuous flooding treatments gradually decreased, and there was no significant difference on day 78. In the soil with a low microbial biomass carbon content, the cumulative CO2 emissions of the dry-wet treatment on day 78 was still significantly lower than that of the continuous flooded treatment. The soils with a low microbial biomass carbon content showed a faster CO2 emission rate at the beginning of the incubation period (first 20 d), which was 1.1-6.1 times greater than that of the high microbial biomass carbon soils owing to their high soil dissolved organic carbon (DOC) content, and the CO2 emission rate then gradually decreased until it was below that of the soil with a high microbial biomass carbon content. The soil organic carbon mineralization rate became stable later in the incubation period (days 45-78). The stable mineralization rate of the high microbial biomass carbon soil was 20%-30% higher than that of the low microbial biomass carbon soil. The multiple regression analysis results showed that the decrease in the soil DOC content (ΔDOC) and the increase in the Fe2+ content (ΔFe2+) significantly affected the change in cumulative CO2 emissions (ΔCO2) under continuous flooding conditions, but had no effect on ΔCO2 during the flooding stage of the dry-wet treatment. The correlation analysis showed that the daily CO2 emission rate of soils with high microbial biomass carbon was significantly positively correlated with glucosidase activity under dry-wet treatment and significantly negatively correlated with acetylglucosaminidase (NAG) and peroxidase activities under continuous flooding treatment. In the low microbial biomass carbon soils, the daily CO2 emission rate of the continuous flooding treatment was negatively correlated with the NAG activity, but showed no correlation with enzyme activities under dry-wet management. In summary, the cumulative CO2 emissions of dry-wet treatment were lower than those of continuous flooding treatment, and the difference was significant in soils with low microbial biomass carbon. The size of the soil microbial biomass determined the level of the stable soil organic carbon mineralization rate. The amount of soluble organic carbon and iron reduction affected the soil CO2 emissions under continuous flooding conditions, and the soil water conditions affected the daily CO2 emission rate and its key influencing enzymes. This study provides data and theoretical support for the carbon cycle and carbon sequestration potential in paddy soil.


Assuntos
Oryza , Solo , Biomassa , Carbono , Microbiologia do Solo , Água
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