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1.
Front Microbiol ; 13: 773487, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35464911

RESUMO

The topography and hydrography around seamounts have a strong influence on plankton biogeography. The intrinsic properties of various biological taxa inherently also shape their distribution. Therefore, it is hypothesized that different pelagic groups respond differently to effects of seamounts regarding their distribution and connectivity patterns. Herein, bacterial, protist, and fungal diversity was investigated across the water column around the Kocebu Guyot in the western Pacific Ocean. A higher connectivity was detected for bacteria than for protists and an extremely low connectivity for fungi, which might be attributed to parasitic and commensal interactions of many fungal taxa. The seamount enhanced the vertical connectivity of bacterial and protist communities, but significantly reduced protist connectivity along horizontal dimension. Such effects provide ecological opportunities for eukaryotic adaption and diversification. All the bacterial, protist, and fungal communities were more strongly affected by deterministic than stochastic processes. Drift appeared to have a more significant role in influencing the fungal community than other groups. Our study indicates the impact of seamounts on the pelagic community distribution and connectivity and highlights the mechanism of horizontally restricted dispersal combined with vertical mixing, which promotes the diversification of eukaryotic life.

2.
Artigo em Inglês | MEDLINE | ID: mdl-35462566

RESUMO

PURPOSE: This study aimed to compare the performance of [68Ga]Ga-DOTA-FAPI-04 and [18F]FDG PET/CT in the evaluation of primary and metastatic lesions of gastric cancer. METHODS: Fifty-six patients with histologically proven gastric carcinomas were enrolled in this study, including 45 patients for staging and 11 patients for restaging after surgery. Each patient underwent both [18F]FDG and [68Ga]Ga-DOTA-FAPI-04 PET/CT within 1 week. The activity of tracer accumulation in lesions was assessed by maximum standardized uptake value (SUVmax) and TBR (lesions SUVmax/ascending aorta SUVmean). Histological workup served as a standard of reference. If tissue diagnosis was not applicable, the follow-up data including the results of laboratory tests and medical imaging could also serve as a reference. RESULTS: [68Ga]Ga-DOTA-FAPI-04 PET/CT was comparable to [18F]FDG on detecting primary tumors and lymph node (LN) metastases, whereas [68Ga]Ga-DOTA-FAPI-04 outperformed [18F]FDG in detecting peritoneal (159 vs. 47, P < 0.001) and bone metastases (64 vs. 55, P = 0.003) by the lesion-based analysis. [68Ga]Ga-DOTA-FAPI-04 showed higher SUVmax (10.3 vs. 8.1, P = 0.004) and TBR (11.6 vs. 5.8, P < 0.001) in primary tumor, and higher TBR in LN involvement (8.0 vs. 3.7, P < 0.001) and peritoneal metastases (8.1 vs. 3.2, P < 0.001), compared with [18F]FDG PET/CT. The specificity and positive predictive value of [68 Ga]Ga-DOTA-FAPI-04 were significantly higher than that of [18F]FDG (100.0% vs. 97.7%, P < 0.001; 100.0% vs. 57.1%, P = 0.001) in determining the LN status. [68Ga]Ga-DOTA-FAPI-04 was comparable to [18F]FDG in evaluating N-staging (47.1% vs. 23.5%, P = 0.282). [68Ga]Ga-DOTA-FAPI-04 PET/CT detected more positive recurrent lesions in all restaging patients and showed clearer tumor delineation. Two patients underwent follow-up [68Ga]Ga-DOTA-FAPI-04 PET/CT scans after chemotherapy, which both showed remission. CONCLUSIONS: [68Ga]Ga-DOTA-FAPI-04 PET/CT can better evaluate primary gastric cancer and metastatic lesions in the peritoneum, abdominal LNs, and bone. Furthermore, [68Ga]Ga-DOTA-FAPI-04 PET/CT provided more information for patients with recurrent disease and had the potential in monitoring response to treatment.

3.
Front Genet ; 13: 787734, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35360844

RESUMO

Craniosynostosis is one of the most common craniofacial deformities demanding surgical treatment in infancy. LncRNA HOTAIR has verified its important role in osteogenesis and osteoarthritis. However, whether HOTAIR plays an essential role in the development of craniosynostosis is still unclear. In this study, we aimed to investigate the molecular role of HOTAIR in the osteoclast function and development of craniosynostosis.For osteoclast differentiation, RAW264.7 cells were induced by 50 ng/ml of RANKL and 10 ng/mL M-CSF, followed by TRAP staining. Cell proliferation and apoptosis were assayed by the CCK-8 kit and Annexin V-FITC apoptosis detection kit, respectively. The expression of HOTAIR was determined in PBMCs by qRT-PCR. Protein levels of all those involved genes were measured by Western blot assay. A luciferase reporter assay was used to determine the miRNA target validation. The HOTAIR expression in PBMCs from children with craniosynostosis was significantly downregulated. The results of cell proliferation and apoptosis assays indicated that silencing of HOTAIR could inhibit osteoclast differentiation and increase cell apoptosis. Moreover, the luciferase reporter assay revealed that the regulatory axis and HOTAIR-miR-152-CAMKIIα were the regulatory mechanisms of HOTAIR in the osteoclast function and development of craniosynostosis.In this study, our data showed that HOTAIR could promote osteoclast differentiation by binding miR-152. Furthermore, the HOTAIR/HOTAIR-miR-152-CAMKIIα axis was found to regulate osteoclast differentiation. These results indicate that the HOTAIR plays a crucial role in the development of osteoclasts.

4.
Stem Cell Res Ther ; 13(1): 114, 2022 03 21.
Artigo em Inglês | MEDLINE | ID: mdl-35313986

RESUMO

BACKGROUND: The progression of Biliary Atresia (BA) is associated with the number of reactive ductular cells (RDCs) whose heterogeneity in origin and evolution in humans remains unknown. SOX9-positive liver progenitor-like cells (LPLCs) have been shown to participate in RDCs and new hepatocyte formation during cholestatic liver regeneration in an animal model, which implies the possibility that hepatocyte-reprogrammed LPLCs could be a source of RDCs in BA. The present study aimed to elucidate the characteristics of SOX9-positive LPLCs in BA for exploring new possible therapeutic targets by manipulating the bi-differentiation process of LPLCs to prevent disease progression. METHODS: Twenty-eight patients, including 24 patients with BA and 4 patients with Congenital Choledochal Cyst as the control group, were retrospectively recruited. Liver biopsy samples were classified histologically using a 4-point scale based on fibrosis severity. LPLCs were detected by SOX9 and HNF4A double positive staining. Single immunohistochemistry, double immunohistochemistry, and multiple immunofluorescence staining were used to determine the different cell types and characteristics of LPLCs. RESULTS: The prognostic predictors of BA, namely total bile acid (TBA), RDCs, and fibrosis, were correlated to the emergence of LPLCs. SOX9 and HNF4A double-positive LPLCs co-stained rarely with relevant markers of portal hepatic progenitor cells (portal-HPCs), including CK19, CK7, EPCAM, PROM1 (CD133), TROP2, and AFP. Under cholestasis conditions, LPLCs acquired superior proliferation and anti-senescence ability among hepatocytes. Moreover, LPLCs arranged as a pseudo-rosette structure appeared from the periportal parenchyma to the portal region, which implied the differentiation from hepatocyte-reprogrammed LPLCs to RDCs with the progression of cholestasis. CONCLUSIONS: LPLCs are associated with disease progression and prognostic factors of BA. The bipotent characteristics of LPLCs are different from those of portal-HPCs. As cholestasis progresses, LPLCs appear to gain superior proliferation and anti-senescence ability and continually differentiate to RDCs.


Assuntos
Atresia Biliar , Colestase , Fatores de Transcrição SOX9 , Atresia Biliar/complicações , Atresia Biliar/metabolismo , Atresia Biliar/patologia , Colestase/complicações , Colestase/patologia , Humanos , Fígado/metabolismo , Regeneração Hepática , Estudos Retrospectivos , Fatores de Transcrição SOX9/genética
5.
J Clin Transl Hepatol ; 10(1): 6-16, 2022 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-35233368

RESUMO

BACKGROUND AND AIMS: Metabolic dysfunction-associated fatty liver disease (MAFLD) is a new concept, proposed in 2020; however, its applicability in Asia populations has yet to be evaluated. Therefore, we aimed to compare the difference in epidemiological and clinical characteristics between MAFLD and non-alcoholic fatty liver disease (NAFLD) among Asian populations. METHODS: Based on the Jinchang cohort, 30,633 participants were collected. The prevalence and incidence of MAFLD and NAFLD were used to analyze the epidemic characteristics and its overlapping effects. In addition, the corresponding clinical characteristics of the two diagnostic criteria populations were compared. RESULTS: The prevalence rates of MAFLD and NAFLD were 21.03% and 18.83%, respectively. After an average 2.28-year follow-up, the incidence densities of MAFLD and NAFLD were 41.58 per 1,000 person-years and 37.69 per 1,000 person-years, respectively. With the increase of baseline age, body mass index (BMI), and waist circumference (WC) levels, the prevalence and incidence of MAFLD and NAFLD were on the rise (all p trend<0.05). Among the total patients diagnosed at baseline or follow-up, most patients had both MAFLD and NAFLD, accounting for 78.84% and 82.88%, respectively. Compared with NAFLD, MAFLD patients had greater proportions of males and metabolic diseases (diabetes, dyslipidemia), and had higher BMI, WC, liver enzymes, blood glucose, and lipid levels in the baseline diagnosis patients (p<0.05). Additionally, lean MAFLD patients had higher metabolic disorders than lean NAFLD patients (p<0.05). CONCLUSIONS: Compared with NAFLD, the newly proposed definition of MAFLD is more practical and accurate, and it can help identify more fatty liver patients with high-risk diseases.

6.
Front Immunol ; 13: 824178, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35237270

RESUMO

The prevalence of CRF07_BC is 39.7% and has become the most infectious HIV strain in China. To study the transmission and diffusion trajectory of CRF07_BC in China and to prevent further expansion of its transmission. A total of 16,635 sequences of the CRF07_BC pol gene were collected from 1997-2020. We characterized the gene subtypes according to a phylogenetic tree analysis. A 0.50% molecular network was constructed to analyze the transmission relationship among different provinces for CRF07_BC and its two epidemic clusters. Spatial and temporal propagation characteristics were analyzed according to phylogeographic analysis. Finally, we evaluated the differences in transmission of CRF07_BC-O, and CRF07_BC-N. Our dataset included 8,816 sequences of CRF07_BC-N and 7,819 sequences of CRF07_BC-O. There were 7,132 CRF07_BC sequences in the molecular network, and the rate of clustered was 42.9%. Compared to CRF07_BC-O, CRF07_BC-N showed significantly (P<0.001) higher transmission-specific rates. CRF07_BC originated among injecting drug users (IDUs), and spread to men who have sex with men (MSMs) and heterosexual individuals (HETs), while MSMs also transmitted directly to HETs. CRF07_BC-O and CRF07_BC-N were prevalent in Xinjiang and Sichuan, respectively, before spreading interprovincially. In modern China, CRF07_BC-N occurs in five of the major economic zones. The CRF07_BC strain, which has contributed to the highest number of HIV infections in China, is divided into two epidemic clusters. Compared with CRF07_BC-O, risk of transmission is much greater in CRF07_BC-N, which is predominantly prevalent in economically developed provinces, and both MSMs and IDUs have transmitted this epidemic cluster to HETs. High-resolution, large-scale monitoring is a useful tool in assessing the trend and spread of the HIV epidemic. The rapidly developing economy of China requires an equally rapid response to the prevention and control of infectious diseases.


Assuntos
Infecções por HIV , HIV-1 , Minorias Sexuais e de Gênero , China/epidemiologia , Infecções por HIV/epidemiologia , HIV-1/genética , Homossexualidade Masculina , Humanos , Masculino , Filogenia
7.
Eur Radiol ; 2022 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-35352157

RESUMO

OBJECTIVE: To evaluate the potential value of [68Ga]Ga-labelled fibroblast activation protein inhibitor ([68Ga]Ga-FAPI) positron emission tomography/computed tomography (PET/CT) in preoperative staging for patients with oral squamous cell carcinoma (OSCC) as compared to 2-[18F]fluoro-2-deoxy-D-glucose (2-[18F]FDG) PET/CT. METHODS: Thirty-six treatment-naïve patients with OSCC who underwent 2-[18F]FDG and [68Ga]Ga-FAPI PET/CT for preoperative staging were enrolled. The maximum standardised uptake value (SUVmax) of the primary tumour and suspected cervical metastatic lymph nodes, and the tumour-to-background ratio (TBR) of the primary tumour, were measured. The accuracy of two imaging modalities for preoperative diagnosis of metastatic lymph nodes was analysed. Histopathology served as the standard of reference. RESULTS: Thirty-seven primary lesions of 36 patients were accurately detected by both [68Ga]Ga-FAPI and 2-[18F]FDG PET/CT. Regarding primary tumours, the SUVmax and TBR of the two imaging modalities in stage T3-T4 were significantly higher than those of stage T1-T2 (all p < 0.05). On the patient analysis, the accuracy for the evaluation of N1-N3 neck status was 52.6% (10/19) for [68Ga]Ga-FAPI PET/CT and 57.9% (11/19) for 2-[18F]FDG PET/CT. Notably, the accuracy for the evaluation of the N0 neck status between [68Ga]Ga-FAPI and 2-[18F]FDG PET/CT was 100% (17/17) and 29% (5/17), respectively. Based on the patient, neck side and neck level, [68Ga]Ga-FAPI PET/CT resulted in higher specificity and accuracy in diagnosing metastatic neck lymph nodes than 2-[18F]FDG PET/CT (all p < 0.05). CONCLUSION: [68Ga]Ga-FAPI PET/CT is a promising tool for preoperative staging of OSCC, and appears to reduce the false positivity seen with 2-[18F]FDG PET/CT for the detection of neck lymph node metastases. KEY POINTS: • [68Ga]Ga-FAPI PET/CT is a promising tool targeting cancer-associated fibroblasts with comparable diagnostic performance to 2-[18F]FDG PET/CT for identifying the primary lesions of OSCC. • [68Ga]Ga-FAPI PET/CT showed higher specificity and accuracy for the evaluation of neck lymph node metastases of OSCC than 2-[18F]FDG PET/CT, especially for N0 neck status.

8.
Clin Transl Oncol ; 2022 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-35118587

RESUMO

PURPOSE: Translocation renal cell carcinoma (tRCC) is a subtype that occurs predominantly in children and young individuals. Metastatic tRCC occurring in young patients is more aggressive than that occurring in older patients, and there are still no effective therapies. Organoids can mimic original tissues and be assessed by high-throughput screening (HTS). We aimed to utilize patient-derived organoids and HTS to screen drugs that can be repurposed for metastatic tRCC with PRCC-TFE3 fusion. METHODS: Tumor tissues were obtained from treatment-naïve metastatic tRCC patients who underwent surgery. Histopathology and fluorescence in situ hybridization (FISH) confirmed the tRCC. Organoids derived from the dissected tissues were cultured and verified by FISH and RNA-seq. HTS was performed to seek promising drugs, and potential mechanisms were explored by RNA-seq and cell-based studies. RESULTS: We successfully established a metastatic tRCC organoid with PRCC-TFE3 fusion, a common fusion subtype, and its characteristics were verified by histopathology, FISH, and RNA-seq. An HTS assay was developed, and the robustness was confirmed. A compound library of 1816 drugs was screened. Eventually, axitinib, crizotinib, and JQ-1 were selected for further validation and were found to induce cell cycle arrest and apoptosis. RNA-seq analyses of posttreatment organoids indicated that crizotinib induced significant changes in autophagy-related genes, consistent with the potential pathogenesis of tRCC. CONCLUSIONS: We established and validated organoids derived from tissues dissected from a patient with metastatic tRCC with PRCC-TFE3 fusion and achieved the HTS process for the first time. Crizotinib might be a targeted therapy worthy of exploration in the clinic for metastatic tRCC with PRCC-TFE3 fusion. Such organoid and HTS assays may represent a promising model system in translational research assisting in the development of clinical strategies.

9.
Ann Surg ; 2022 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-35170539

RESUMO

OBJECTIVE: To evaluate the efficacy and side effects of additional postoperative steroid therapy for type 3 biliary atresia (BA) versus the current routine care. SUMMARY BACKGROUND DATA: Whether steroid therapy post-Kasai portoenterostomy improves the outcomes of biliary atresia remains controversial. Clinical evidence from two randomized trials in the UK and USA do not support the routine use of steroid in the treatment of biliary atresia. METHODS: In this open-label randomized controlled trial, patients with type 3 BA were randomized to routine postoperative treatment with or without 10-12weeks of adjuvant steroid treatment. The primary outcome was the postoperative jaundice clearance rate with native liver at 6 months. The secondary outcomes included postoperative jaundice clearance rate at 3, 12 and 24 months, survival with native liver at 12 and 24 months, and serious adverse events within 3 months. RESULTS: Overall, 200 participants were randomized and allocated into either steroid or control group (n = 100/group). The proportion of participants that are jaundice free without liver transplantation was significantly higher in the steroid group than in the control group at 6 months (54.1% vs 31.0%, P = 0.0015). The native liver survival rate was higher postoperatively in the steroid group than in the control group at 12 (66.3% vs 50.0%, P = 0.02) and 24 (57.1% vs 40.0%, P = 0.02) months. The survival time with native liver was significantly longer in the steroid group than in the control group (median survival, steroid vs control: not reached vs 1.21 years, P = 0.02). There were no significant differences between the two groups in the mean occurrence of serious adverse events within 3 months (steroid vs control: 0.63 vs 0.45, P = 0.20). CONCLUSIONS: Postoperative adjuvant steroid intervention improved bile drainage and survival with native liver in type 3 BA patients, without increasing early-stage serious adverse events.

10.
Food Chem ; 379: 132078, 2022 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-35063846

RESUMO

Torreya grandis has high economic and nutritional value due to the high nutrients in its kernels. The kernels of different development stages vary enormously in their amino acids content. However, the molecular basis and the regulatory mechanism of amino acid biosynthesis remain unclear. Here, transcriptome and metabolome analysis were performed. Correlation analysis result showed that 4 unigenes were significantly and positively correlated with at least 10 amino acids. The full length CDS of 2 unigenes (TgDAHP2 and TgASA1) were successfully cloned from the 4 unigenes for DAHP, ASA and CITS. Subcelluar localization analysis showed that both TgDAHP2 and TgASA1 were localized to the chloroplast. Overexpression of TgDAHP2 and TgASA1 in Arabidopsis can greatly increase the content of most amino acids. Moreover, 3 transcription factors were found to positively regulate the expression of TgASA1. This research contributes to understand the molecular regulatory mechanisms of amino acid biosynthesis in T. grandis.


Assuntos
Taxaceae , Transcriptoma , Aminoácidos/genética , Cloroplastos , Metaboloma
11.
Clin Nucl Med ; 47(5): 467-468, 2022 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-35025798

RESUMO

ABSTRACT: A 43-year-old woman with history of papillary thyroid cancer status post total thyroidectomy and neck dissection and multiple radioiodine therapy developed dyspnea and cough. CT scan of the chest showed left pleural thickening and pleural effusion. The pathology from pleural biopsy demonstrated the metastases from papillary thyroid cancer. 68Ga-fibroblast activation protein inhibitor PET/CT showed inhomogeneously increased uptake of fibroblast activation protein inhibitor in the thickened pleura.


Assuntos
Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Neoplasias da Glândula Tireoide , Adulto , Feminino , Humanos , Radioisótopos do Iodo , Pleura , Quinolinas , Câncer Papilífero da Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/diagnóstico por imagem
12.
Cerebrovasc Dis ; 51(2): 225-234, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34644707

RESUMO

INTRODUCTION: It is not clear whether serum uric acid (SUA) levels and their changes over time are associated with the risk of stroke. A 7-year prospective cohort study in northwest China was conducted to analyze effects of SUA and their changes on the risk of stroke. METHODS: A total of 23,262 individuals without cardiovascular disease in the Jinchang cohort were followed up for an average of 5.26 years. The Cox proportional hazard model was used to estimate the hazard ratios (HRs) and 95% confidence interval (95% CI) of stroke incidence to SUA and relative changes in SUA. Sensitivity analysis was performed after controlling the effect of renal insufficiency. RESULTS: Baseline SUA and relative changes in SUA were positively correlated with the incidence of stroke in both males and females (p for overall association <0.0001). Stroke risk increased by 4.6% per 10% increase in the relative change of SUA (HR = 1.046, 95% CI, 1.007-1.086). The fully adjusted regression analysis demonstrated that only the large gain (>30%) in SUA was associated with an increased risk of stroke by 36.5% (95% CI, 1.8-83.0%), compared with the reference group (participants within ±10% changes in SUA). The same trend was observed in people with normal baseline SUA. In the unadjusted model, the risk of stroke associated with elevated SUA was significantly higher in the hyperuricemia group than in the normal SUA group. CONCLUSION: High initial SUA concentration and an increase in SUA concentration over time would increase the risk of stroke, and this means that there is no safe increase in SUA.


Assuntos
Hiperuricemia , Acidente Vascular Cerebral , China/epidemiologia , Estudos de Coortes , Feminino , Humanos , Hiperuricemia/diagnóstico , Hiperuricemia/epidemiologia , Masculino , Estudos Prospectivos , Fatores de Risco , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/epidemiologia , Ácido Úrico
13.
Clin Nucl Med ; 47(3): 239-240, 2022 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-34619704

RESUMO

ABSTRACT: A 28-year-old woman presented with abdominal pain, bowel dysfunction, and weight loss for 3 months. 18F-FDG PET/CT revealed multiple hypermetabolic lesions in the intestines and peritoneal thickening/caking with moderate FDG activity. 68Ga-FAPI PET/CT showed intense FAPI uptake in the aforementioned FDG-avid lesions and a larger number of abnormal foci with intense FAPI uptake in the peritoneum than that shown in 18F-FDG images. Endoscopy-guided biopsy from the colonic mucosa was consistent with tuberculosis. The positive findings of 68Ga-FAPI in the current case highlighted that 68Ga-FAPI may have value in the evaluation of intestinal tuberculosis.


Assuntos
Quinolinas , Tuberculose , Adulto , Feminino , Fluordesoxiglucose F18 , Humanos , Peritônio , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada
14.
Int J Urol ; 29(3): 212-220, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34847622

RESUMO

OBJECTIVES: Metastatic renal cell carcinoma can occur synchronously or metachronously. We characterized the time from diagnosis to systematic therapy as a categorical variable to analyze its effect on the overall survival and first-line treatment efficacy of metastatic renal cell carcinoma patients. METHODS: We initially enrolled 949 consecutive metastatic renal cell carcinoma patients treated with targeted therapies retrospectively from December 2005 to December 2019. X-tile analysis was used to determine cut-off values of time from diagnosis to systematic therapy referring to overall survival. Patients were divided into different groups based on the time from diagnosis to systematic therapy and then analyzed for survival. RESULTS: Of 358 eligible patients with metastatic renal cell carcinoma, 125 (34.9%) had synchronous metastases followed by cytoreductive nephrectomy, and 233 (65.1%) had metachronous metastases. A total of 28 patients received complete metastasectomy. Three optimal cut-off values for the time from diagnosis to systematic therapy (months) - 1.1, 7.0 and 35.9 - were applied to divide the population into four groups: the synchro group (time from diagnosis to systematic therapy ≤1.0), early group (1.0 < time from diagnosis to systematic therapy ≤ 7.0), intermediate group (7.0 < time from diagnosis to systematic therapy < 36.0) and late group (time from diagnosis to systematic therapy ≥36.0). The targeted therapy-related overall survival (P < 0.001) and progression-free survival (P < 0.001) values were significantly different among the four groups. Patients with longer time from diagnosis to systematic therapy had better prognoses and promising efficacy of targeted therapy. With the prolongation of time from diagnosis to systematic therapy, complete metastasectomy was more likely to achieve and bring a better prognosis. CONCLUSIONS: The time from diagnosis to systematic therapy impacts the survival of metastatic renal cell carcinoma patients treated with targeted therapy. The cutoff points of 1, 7 and 36 months were statistically significant. The statistical boundaries might be valuable in future model establishment.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Carcinoma de Células Renais/patologia , Seguimentos , Humanos , Neoplasias Renais/patologia , Nefrectomia , Prognóstico , Estudos Retrospectivos
15.
Ann Hematol ; 101(1): 91-97, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34605949

RESUMO

Extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) lymphoma is a type of low-grade malignant B-cell lymphoma. The aim of this study was to investigate the clinicopathological characteristics of thymic MALT lymphoma. We analyzed the clinical, morphological, immunophenotypical, cytogenetic, and molecular characteristics of 11 cases of thymic MALT lymphoma. The relevant literature was also reviewed. The median age of the 11 patients was 50 (range: 33-60). There was a female predominance with a female-to-male ratio of 10:1. Three patients presented with Sjögren syndrome, autoimmune thrombocytopenia purpura, and type B1 thymoma, respectively. Microscopically, thymic MALT lymphoma was characterized by epithelium-lined cysts that were surrounded by small lymphocytes, centrocyte-like cells, and monocytoid B-cells. Plasmacytic differentiation was observed in two cases. The tumor cells expressed CD20, CD79α, and BCL2. Clonal immunoglobulin genes were detected in all 8 examined cases. Fluorescence in situ hybridization (FISH) for 18q21 was performed in 7 cases, and no translocations involving 18q21 were found. Targeted gene sequencing was performed in five cases with available DNA samples, and TNFAIP3, CARD11, IGLL5, and CCND3 mutations were identified. Thymic MALT lymphoma is a rare type of B cell malignancy with a female predominance and excellent clinical outcomes. Molecular aberrations involving the NF-κB pathway are frequent in thymic MALT lymphoma, suggesting that dysregulation of the NF-κB pathway is an important mechanism underlying the pathogenesis of thymic MALT lymphoma.


Assuntos
Linfoma de Zona Marginal Tipo Células B/genética , Neoplasias do Timo/genética , Adulto , Feminino , Rearranjo Gênico , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Hibridização in Situ Fluorescente , Linfoma de Zona Marginal Tipo Células B/patologia , Masculino , Pessoa de Meia-Idade , Mutação , Neoplasias do Timo/patologia , Translocação Genética
16.
Food Chem ; 374: 131558, 2022 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-34794838

RESUMO

The kernel of Torreya grandis (T. grandis) is a rare nut with a variety of bioactive compounds. Flavonoids are a very important class of bioactive compounds with high antioxidant activity in T. grandis kernels. However, the flavonoid compositions which mainly contribute to antioxidant capacity and the molecular basis of flavonoid biosynthesis in T. grandis remain unclear. Here, transcriptome sequencing and metabolomics analysis for kernels were performed. In total, 124 flavonoids were identified. Among them, 9 flavonoids were highly correlated with antioxidant activity. Furthermore, unigenes encoding CHS, DFR and ANS showed significant correlation with the 9 flavonoids. Transient overexpression of TgDFR1 in tobacco leaves resulted in increased antioxidant activity. Moreover, several transcription factors from MYB, bHLH and bZIP families were identified by co-expression assay, suggesting that they may regulate flavonoid biosynthesis. Our findings provide a molecular basis and new insights into the flavonoid biosynthesis in T. grandis kernels.


Assuntos
Taxaceae , Transcriptoma , Flavonoides , Regulação da Expressão Gênica de Plantas , Humanos , Metabolômica , Proteínas de Plantas/metabolismo , Fatores de Transcrição/metabolismo
17.
J Hazard Mater ; 425: 127942, 2022 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-34902725

RESUMO

Antibiotic resistance genes (ARGs) are receiving increasing concerns due to the antibiotic resistance crisis. Nevertheless, little is known about the spatial behavior and sources of extracellular ARGs (eARGs) in the chlorinated drinking water distribution systems (DWDSs). Here, tap water was continuously collected to reveal the occurrence of both eARGs and intracellular ARGs (iARGs) along a chlorinated DWDS. Afterward, the correlation between eARGs, eDNA-releasing communities, and communities of planktonic bacteria was further analyzed. The eARG concentration decreased significantly, whereas the proportion of vanA and blaNDM-1 increased. Further, the diversity of the eDNA-releasing community increased markedly with increasing distance from the drinking water treatment plant (DWTP). Moreover, the dominant eDNA-releasing bacteria shifted from Acinetobacter, Pseudomonas, and Methylobacterium-Methylorubrum in finished water from the DWTP to Bacteroides, Faecalibacterium, Staphylococcus, and Parabacteroides in the DWDS. In terms of eARG source, thirty genera were significantly correlated with seven types of eARGs that resulted from the lysis of dead planktonic bacteria and detached biofilms. Conversely, the iARGs concentration increased, whereas the biodiversity of the planktonic bacteria community decreased in the sampling points along the DWDSs. Our findings provide critical insights into the spatial behavior and sources of eARGs, highlighting the health risks associated with ARGs in DWDSs.


Assuntos
Água Potável , Purificação da Água , Antibacterianos/farmacologia , Resistência Microbiana a Medicamentos/genética , Genes Bacterianos , Comportamento Espacial , Águas Residuárias
18.
Support Care Cancer ; 30(1): 413-421, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34302546

RESUMO

BACKGROUND: Few mortality-scoring models are available for solid tumor patients who are predisposed to develop Escherichia coli-caused bloodstream infection (ECBSI). We aimed to develop a mortality-scoring model by using information from blood culture time to positivity (TTP) and other clinical variables. METHODS: A cohort of solid tumor patients who were admitted to hospital with ECBSI and received empirical antimicrobial therapy was enrolled. Survivors and non-survivors were compared to identify the risk factors of in-hospital mortality. Univariable and multivariable regression analyses were adopted to identify the mortality-associated predictors. Risk scores were assigned by weighting the regression coefficients with corresponding natural logarithm of the odds ratio for each predictor. RESULTS: Solid tumor patients with ECBSI were distributed in the development and validation groups, respectively. Six mortality-associated predictors were identified and included in the scoring model: acute respiratory distress (ARDS), TTP ≤ 8 h, inappropriate antibiotic therapy, blood transfusion, fever ≥ 39 °C, and metastasis. Prognostic scores were categorized into three groups that predicted mortality: low risk (< 10% mortality, 0-1 points), medium risk (10-20% mortality, 2 points), and high risk (> 20% mortality, ≥ 3 points). The TTP-incorporated scoring model showed excellent discrimination and calibration for both groups, with AUC being 0.833 vs 0.844, respectively, and no significant difference in the Hosmer-Lemeshow test (6.709, P = 0.48) and the chi-square test (6.993, P = 0.46). Youden index showed the best cutoff value of ≥ 3 with 76.11% sensitivity and 79.29% specificity. TTP-incorporated scoring model had higher AUC than no TTP-incorporated model (0.837 vs 0.817, P < 0.01). CONCLUSIONS: Our TTP-incorporated scoring model was associated with improving capability in predicting ECBSI-related mortality. It can be a practical tool for clinicians to identify and manage bacteremic solid tumor patients with high risk of mortality.


Assuntos
Neoplasias , Sepse , Escherichia coli , Mortalidade Hospitalar , Humanos , Prognóstico , Estudos Retrospectivos , Fatores de Risco
19.
Zool Res ; 43(1): 52-63, 2022 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-34821086

RESUMO

The ability to sense temperature changes is crucial for mammalian survival. Mammalian thermal sensing is primarily carried out by thermosensitive transient receptor potential channels (Thermo-TRPs). Some mammals hibernate to survive cold winter conditions, during which time their body temperature fluctuates dramatically. However, the underlying mechanisms by which these mammals regulate thermal responses remain unclear. Using quantitative real-time polymerase chain reaction (qRT-PCR) and the Western blotting, we found that Myotis ricketti bats had high levels of heat-activated TRPs (e.g., TRPV1 and TRPV4) during torpor in winter and cold-activated TRPs (e.g., TRPM8 and TRPC5) during active states in summer. We also found that laboratory mice had high mRNA levels of cold-activated TRPs (e.g., Trpm8 and Trpc5) under relatively hot conditions (i.e., 40 °C). These data suggest that small mammals up-regulate the expression of cold-activated TRPs even under warm or hot conditions. Binding site analysis showed that some homeobox (HOX) transcription factors (TFs) regulate the expression of hot- and cold-activated TRP genes and that some TFs of the Pit-Oct-Unc (POU) family regulate warm-sensitive and cold-activated TRP genes. The dual-luciferase reporter assay results demonstrated that TFs HOXA9, POU3F1, and POU5F1 regulate TRPC5 expression, suggesting that Thermo-TRP genes are regulated by multiple TFs of the HOX and POU families at different levels. This study provides insights into the adaptive mechanisms underlying thermal sensing used by bats to survive hibernation.


Assuntos
Quirópteros , Temperatura Alta , Estações do Ano , Canais de Cátion TRPC , Animais , Quirópteros/genética , Feminino , Hibernação/genética , Masculino , Camundongos , Canais de Cátion TRPC/genética , Canais de Cátion TRPV/genética
20.
Front Pediatr ; 9: 751204, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34858903

RESUMO

Aims: Cholangitis in biliary atresia (BA), which accelerates liver fibrosis progression, is among the most common serious complications after Kasai surgery; however, its etiology remains elusive. Gut microbiome migration may contribute to post-Kasai cholangitis. Further, there is no appropriate model of BA post-Kasai cholangitis for use in investigation of its pathogenesis. Methods: We explored the characteristics of gut microbiome in patients with BA before and after Kasai procedure based on 16S rDNA sequencing. We isolated the dominant strain from patient stool samples and established an in vitro model by infecting patient-derived liver organoids. Bulk RNA-seq was performed, and we conducted qPCR, ELISA, and western blot to explore the mechanism of fibrosis. Results: Gut microbiome diversity was lower in patients after, relative to before, Kasai procedure, while the relative abundance of Klebsiella was higher. Patients who developed cholangitis within 1 month after discharge tended to have simpler gut microbiome composition, dominated by Klebsiella. Klebsiella pneumoniae (KPN) was isolated and used for modeling. RNA-seq showed that BA liver organoids expressed markers of hepatic progenitor cells (KRT19, KRT7, EPCAM, etc.) and that organoids were more stable and less heterogeneous among individuals than liver tissues. After infection with KPN, gene expression patterns in BA liver organoids were enriched in pathways related to infection, apoptosis, and fibrosis. Preliminary experiments indicated the presence of IL-13/TGF-ß1-mediated fibrosis in post-Kasai cholangitis. Conclusions: Our findings using a newly-developed model, demonstrate a key role for Klebsiella, and a potential mechanism underlying fibrosis in post-Kasai cholangitis, mediated by the IL-13/TGF-ß1 pathway.

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