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1.
Environ Pollut ; 292(Pt B): 118370, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34656677

RESUMO

Benzophenone-1 (BP-1) belongs to personal care product-related contaminants of emerging concern and has been recently reported to induce xenoestrogenic effects. However, the underlying mechanisms leading to the activation of target receptors and subsequent various adverse outcomes remain unclear, which is beneficial to safety and health risk assessment of benzophenone-type ultraviolet filters with their widespread occurrence. Herein, we investigated disrupting effects of BP-1 at environmentally relevant concentrations (10-9-10-6 M) on estrogen receptor (ER) α-associated signaling pathways. Molecular dynamics simulations together with yeast-based assays revealed the steady binding of BP-1 to ERα ligand binding domain (LBD) and hence the observed agonistic activity. BP-1 triggered interaction between ERα and ß-catenin in human SKOV3 ovarian cancer cells and caused translocation of ß-catenin from the cytoplasm to the nucleus, leading to aberrant activation of Wnt/ß-catenin. BP-1 consequently induced dissemination of SKOV3 via regulating epithelial-mesenchymal transitions (EMT) biomarkers including minimally downregulating ZO-1 gene to 78.0 ± 10.1% and maximally upregulating MMP9 gene to 144.1 ± 29.7% and promoted 1.03-1.83 fold proliferation, migration and invasion of SKOV3. We provide the first evidence that the BP-1 activated ERα triggers crosstalk between ERα and Wnt/ß-catenin pathway, leading to the abnormal stimulation and progression of SKOV3 cancer cells.

2.
Sci Total Environ ; 802: 149793, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34454143

RESUMO

Polycyclic aromatic hydrocarbons (PAHs) are epidemiologically associated with cardiovascular diseases characterized by early key events involving in the disruption of endothelial barrier function. Whether PAHs can induce adverse cardiovascular outcome by directly destabilizing endothelial barrier function remains elusive. Herein, we investigated the effect of anthracene (ANT), 9-nitroanthracene (9-NANT), and 9,10-anthraquinone (9,10-AQ) on vascular endothelial barrier functions in human umbilical vein endothelial cells (HUVECs). The integrity of endothelial barrier in HUVECs was disturbed with a 1.15-1.42 fold increase in fluorescein leakage, and 21.8%-58.3% downregulated transendothelial electrical resistance. ANT, 9-NANT and 9,10-AQ promoted paracellular gap formation as revealed by transmission electron microscope. The disrupted cell junctions after 24 h exposure to ANT, 9-NANT and 9,10-AQ at 0.01 µM were indicated by the downregulated mRNA expression of vascular endothelial cadherin (VE-cadherin), zona occludens-1 (ZO-1) and occludin by 33.2%-71.4%, 19.1%-21.0%, and 31.9% respectively, and the downregulated protein expression of ZO-1 and occludin, and by the internalization of VE-cadherin. We demonstrated that ANT and its derivatives at environmentally relevant concentrations induced endothelial barrier dysfunction via the disruption of cell junctions, providing essential in vitro evidence on the association with their adverse cardiovascular outcomes.


Assuntos
Antracenos , Nitratos , Hidrocarbonetos Policíclicos Aromáticos , Antracenos/toxicidade , Células Cultivadas , Células Endoteliais da Veia Umbilical Humana , Humanos , Óxidos de Nitrogênio
3.
Sci Total Environ ; 803: 150043, 2022 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-34525697

RESUMO

Soil is a major reservoir and a secondary source of semi-volatile organic chemicals, while studies on the pollution status of halogenated flame retardants (HFRs) in agricultural soils are limited. In this study, a total of twenty-five chemicals including novel brominated flame retardants (NBFRs), polybrominated diphenyl ethers (PBDEs), and dechlorane plus (DPs) was analyzed in the agricultural soils across China to investigate the occurrence, spatial distribution, potential sources, influencing factors and their associated human health risks. The results showed that BDE-209 (125-130,183 pg/g, dry weight, d.w.) was the most abundant flame retardant of PBDEs, followed by decabromodiphenyl ethane (DBDPE) (9.27-22,864 pg/g, d.w.). Meanwhile, the DPs (anti-DP plus syn-DP) were in the range of ND-1229 pg/g (d.w.), and the range of fanti values (the concentration of anti-DP divided by the sum of the concentrations of two isomers) in this study greatly matched those of commercial products, suggesting the effect of proximity to the source region. The higher levels of HFRs were found in Eastern and Southern regions of China. Spatial distribution implied that e-waste recycling activities and plastic processing have shown more importance in releasing legacy flame retardants (FRs) into the environment than the manufacturing process, while all are important for novel FRs. Correlation analysis between influencing factors and HFRs indicated that the distribution of most pollutants was more affected by anthropogenic source factors than environmental factors. The results of the principal component analysis demonstrated that deca-BDE and its alternative products were the major contributors to the sources of HFRs pollution. Human health risks assessment via oral intake and dermal contact pathways presented that the selected pollutants posed a no-carcinogenic risk to children and adults. It is worth noting that supervision of the disposal process of the NBFRs should be strengthened in the future.


Assuntos
Retardadores de Chama , Compostos Orgânicos Voláteis , Criança , China , Monitoramento Ambiental , Retardadores de Chama/análise , Éteres Difenil Halogenados/análise , Humanos , Solo
4.
Opt Lett ; 46(21): 5473-5476, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34724504

RESUMO

In this Letter, a ring-core erbium-doped fiber (RC-EDF), with a two-layer erbium-doped structure, supporting up to the fourth-order orbital angular momentum (OAM) mode was designed and fabricated for the OAM mode multiplexed amplification. Using the RC-EDF, the amplification of the third- and fourth-order OAM modes with an ultra-low differential mode gain (DMG) has been demonstrated by observing both the modal intensity and phase distribution and measuring the modal gain under the fundamental mode core pumping. The measured average gain of four modes' (OAM±3,1 and OAM±4,1) multiplexed amplification is >19dB, covering the C band, and the DMG is <1dB. Additionally, the gains of two conjugate OAM modes are almost the same under different pump power, regardless of whether they are amplified simultaneously or separately.

5.
Front Oncol ; 11: 750323, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34804937

RESUMO

Chidamide has demonstrated significant clinical benefits for patients with relapsed/refractory (R/R) PTCL in previous studies. This multi-center observational study was aimed to evaluate the objective response rate (ORR), overall survival (OS), and safety of chidamide. From February 2015 to December 2017, 548 patients with R/R PTCL from 186 research centers in China were included in the study. Among the 261 patients treated with chidamide monotherapy, ORR was 58.6% and 55 patients (21.1%) achieved complete response (CR). Among the 287 patients receiving chidamide-containing combination therapies, ORR was 73.2% and 73 patients (25.4%) achieved CR. The median OS of all patients was 15.1 months. The median OS of patients receiving chidamide monotherapy and combination therapies was 433 and 463 days, respectively. These results demonstrate a significant survival advantage of chidamide treatments as compared with international historical records. Common adverse effects (AEs) were hematological toxicities. Most AEs in both monotherapy and combined treatments were grade 1-2. No unanticipated AEs occurred. In conclusion, chidamide-based therapy led to a favorable efficacy and survival benefit for R/R PTCL. Future studies should explore the potential advantage of chidamide treatment combined with chemotherapy.

6.
Opt Express ; 29(22): 34900-34912, 2021 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-34808939

RESUMO

Optical coordinate transformation (OCT) has attracted widespread attention in the field of orbital angular momentum (OAM) (de)multiplexing or manipulation, but the performance of OCT would suffer from its distortion. In this paper, we quantitatively analyze the distortion of OCT from the perspective of ray optics and explain its rationality to work under non-normal incident light. For the special case of log-polar coordinate transformation (LPCT), we use a raytracing assisted optimization scheme to improve its distortion, which is related to a Zernike polynomial based phase compensation. After raytracing optimization, the root mean square error (RMSE) of the focused rays is reduced to 1/5 of the original value and the physical optic simulation also shows great improvement. In the experiment, we use three phase masks which are realized by metasurfaces, the measured results show well consistency with the simulation. Results in this paper have great potential to improve the performance of OCT related applications.

7.
Leuk Lymphoma ; : 1-10, 2021 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-34751093

RESUMO

The utility of circulating tumor DNA (ctDNA) in classifying the cell origin of diffuse large B-cell lymphoma (DLBCL) has not been explored in the Chinese population. In this study, we aimed to investigate the genetic characteristics of DLBCL based on both tumor and ctDNA sequencing and to assess the predictive value of ctDNA in DLBCL. A targeted sequencing panel of 413 genes was applied to tumor biopsies and paired plasma samples obtained from 30 patients with DLBCL before therapeutic intervention (pretreatment). The concordance between plasma genotyping classification and traditional cell-of-origin classification using tumor tissue was 80.0% (20/25). Patients with higher baseline plasma ctDNA levels had poorer survival compared to those with lower ctDNA levels (2-year progression survival rate: 40.0% vs. 80.0%, p = 0.011; 5-year overall survival rate: 30.5% vs. 70.0%, p = 0.004). Collectively, our results demonstrated that pretreatment ctDNA analysis could assist origin determination and prognosis prediction clinically.

8.
Orphanet J Rare Dis ; 16(1): 479, 2021 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-34794461

RESUMO

BACKGROUND: Extranodal NK/T-cell lymphoma of the breast (ENKTL-Breast) is rarely detected in clinical practice, and its clinicopathological features remain unclear. RESULTS: A consecutive 11-year (2010-2020) ENKTL-Breast case series was retrospectively analyzed. Eight cases of ENKTL-Breast were selected, with three primary and five secondary lesions, accounting for 3.5% (8/228) of all breast lymphomas. All patients were female with a median age of 46 years. Lesions presented as solid breast masses (8/8, 100%) and were usually located in the upper outer quadrant of the breast (7/8, 87.5%). B-symptoms were observed in seven (7/8, 87.5%) cases. Two primary ENKTL-Breast cases showed concomitant diseases (IgA nephropathy and chronic active hepatitis B). Histological and immunohistochemical features of ENKTL-Breast were similar to those of ENKTL at other sites. T-cell receptor rearrangement revealed clonality in all examined primary cases (2/2, 100%), but only in one secondary case (1/5, 20%). The disease progressed rapidly in two primary cases and both patients died within 3 and 9 months. For secondary cases, the disease manifested as a disseminated disease, with a median survival time of 6 months. CONCLUSIONS: Our data suggested that ENKTL-Breast clinically mimics breast cancer to some extent, though B-symptoms might serve as a distinguishing factor. ENKTL-Breast is highly aggressive and patients with this disease exhibit a short survival time. Primary ENKTL-Breast tends to originate from activated cytotoxic T-cells, and immune-related diseases may be involved in its pathogenesis and development.

9.
Chem Sci ; 12(42): 14033-14038, 2021 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-34760186

RESUMO

The introduction of deuterium atoms into organic compounds is of importance for basic chemistry, material sciences, and the development of drugs in the pharmaceutical industry, specifically for identification and quantification of metabolites. Hence, methodologies for the synthesis of selectively labelled compounds continue to be a major area of interest for many scientists. Herein, we present a practical and stable heterogeneous copper catalyst, which permits for dehalogenative deuteration via water-gas shift reaction at comparably low temperature. This novel approach allows deuteration of diverse (hetero)aryl halides with good functional group tolerance, and no reduction of the aromatic rings or other easily reducible formyl and cyano groups. Multi-gram experiments show the potential of this method in organic synthesis and medicinal chemistry.

10.
Ann Vasc Surg ; 2021 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-34775019

RESUMO

OBJECTIVES: Spiral saphenous vein grafts (SSVG) or paneled vein grafts (PVG) can be used when the diameter of the autologous great saphenous vein does not match the vessel that needs to be repaired. This study aimed to present early results of complex vascular reconstruction with SSVGs and PVGs in the lower extremities. METHODS: From May 2019 through January 2021, six SSVGs and three PVGs were used for vascular reconstruction in nine patients. Patient data were collected retrospectively, including age, gender, cause of vascular pathology, target vessels, concomitant injury, surgical method, additional surgical methods, and hemodynamic status. The Kaplan-Meier method was used to calculate the rate of freedom from reintervention. RESULTS: Among these patients, seven had trauma, one had graft infection, and one had vascular reconstruction after tumor excision. The mean duration of follow-up was 6 ± 6.6 months (range 1-19 months). The rate of freedom from reintervention for any reason was 77.8% at 1 year. Two patients underwent amputation after vascular reconstruction with patent vascular reconstructions. One of the two amputations was performed because of infection, and the other was due to ischemia >24 hours. The success rate of reconstruction was 100%, and the primary patency rate was 100%. The rate of limb salvage was 77.8%. There was no death, bleeding, embolism, skin ulcers, graft-related complication, or aneurysmal dilation during follow-up. CONCLUSIONS: SSVG and PVG were associated with low infection rates and satisfactory short-term patency rates. These two grafts may be good choices when there is a diameter mismatch in vascular reconstructions.

11.
Environ Chem Lett ; : 1-11, 2021 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-34744548

RESUMO

Despite large decreases of emissions of air pollution during the coronavirus disease 2019 (COVID-19) lockdown in 2020, an unexpected regional severe haze has still occurred over the North China Plain. To clarify the origin of this pollution, we studied air concentrations of fine particulate matter (PM2.5), NO2, O3, PM10, SO2, and CO in Beijing, Hengshui and Baoding during the lockdown period from January 24 to 29, 2020. Variations of PM2.5 composition in inorganic ions, elemental carbon and organic matter were also investigated. The HYSPLIT model was used to calculate backward trajectories and concentration weighted trajectories. Results of the cluster trajectory analysis and model simulations show that the severe haze was caused mainly by the emissions of northeastern non-stopping industries located in Inner Mongolia, Liaoning, Hebei, and Tianjin. In Beijing, Hengshui and Baoding, the mixing layer heights were about 30% lower and the maximum relative humidity was 83% higher than the annual averages, and the average wind speeds were lower than 1.5 m s-1. The concentrations of NO3 -, SO4 2-, NH4 +, organics and K+ were the main components of PM2.5 in Beijing and Hengshui, while organics, K+, NO3 -, SO4 2-, and NH4 + were the main components of PM2.5 in Baoding. Contrary to previous reports suggesting a southerly transport of air pollution, we found that northeast transport caused the haze formation. Supplementary Information: The online version contains supplementary material available at 10.1007/s10311-021-01314-8.

12.
Neurol Sci ; 2021 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-34750685

RESUMO

PURPOSE: Hospital-acquired pneumonia (HAP) is becoming a serious problem in China, especially caused by multi-drug resistant (MDR), which is a risk factor for poor prognosis of intracranial cerebral hemorrhage (ICH). We investigate the risk factors for HAP among patients with ICH and study the antibiotic use and medical costs of MDR infection. METHODS: We performed a retrospective, case-control, parallel study in Xiangya Hospital. Patients included in this study and diagnosed with basal ganglia hemorrhage were admitted between January 2017 and December 2019. RESULTS: Univariate analysis discovered some personal risk factors including gender (p = .002), age (p = .023), and underlying conditions such as diabetes (p = .036), coronary heart disease (p = .009), and renal insufficiency (p = .001). Invasive medical operations including endotracheal intubation, tracheotomy, ventilator use, lumbar puncture, urinary catheter insertion, and peripherally inserted central catheter (PICC) (p < .001 all) were also risk factors for HAP. Binary logistics regression indicated hospital duration, antibiotic exposure, and urinary catheter insertion explained 91.4% of the variance on HAP (p < 0.01). As for the antibiotic treatment, there were no difference in the duration of use days and total dose per patient between MDR and non-MDR group, except for Tigecycline. Antibiotic costs for the MDR group were significantly higher than those for the non-MDR group and no infection group (p < 0.001). CONCLUSION: To better prevent HAP particularly caused by MDR bacteria, we emphasize the aseptic technique especially in the management of equipment in patient care.

13.
J Cancer ; 12(22): 6883-6893, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34659576

RESUMO

Background: Tumor-associated calcium signal transducer 2 (TROP2) is over expressed in various kinds of human cancers and plays important roles in the proliferation, invasion and metastasis of tumor cells. However, the expression and molecular mechanism of TROP2 in thyroid papillary carcinoma (PTC) are unclear. Methods: The expressions of TROP2 in PTC and control tissue were detected by real-time reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry. The proliferation and invasion of PTC cell lines were examined by cell cloning and transwell assays. RNA sequencing analysis and public data analysis were assessed to investigate the potential mechanisms of TROP2 in PTC. Gene correlation analysis was conducted to explore the association between TROP2 and the related gene ISG15 in patients with PTC. Results: The expression of TROP2 was significantly higher in PTC than control. The high expression of TROP2 protein was associated with lymph node metastasis, tumor size and capsular infiltration (P<0.05). SiRNA-mediated TROP2 gene expression silencing can significantly inhibit proliferation and migration of PTC cells. ISG15 decreased in TROP2 siRNA PTC cells and increased in PTC patients significantly. There was a significant correlation between the expression of TROP2 and ISG15 in PTC patients. TROP2 interacted directly with ATP6V1A, CEBPA and SOX5 and then further interacted with the immune genes. TROP2 expression and tumor-infiltrating immune cells were also correlated in thyroid cancer microenvironment. Conclusions: TROP2 promotes the development of PTC. TROP2 expression was correlated with ISG15 and tumor-infiltrating immune cells in thyroid cancer.

14.
Chemosphere ; 288(Pt 2): 132420, 2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34600925

RESUMO

Calcium carbonate oligomers are gel-state precursors that can be crystallized by low-temperature heat treatments to form an inorganic material with a monolithic and continuous structure, this material can effectively solidify/stabilize heavy metals in municipal solid waste incineration fly ash (MSWI FA). Calcium chloride addition achieves FA stabilization/solidification by the formation and polymerization of calcium carbonate oligomers. The effects of calcium, triethylamine (TEA), and water-washing pretreatment on the solidification of heavy metals by the polymer were studied. Consequently, as more calcium was added, the solidification improved. When the ratio of TEA/Ca2+ was increased from 2:1 to 3:1, the solidification efficiency of As and Cd increased, but it decreased when the ratio was continuously increased to 4:1. After the water-washing pre-treatment, the MSWI FA had a significantly improved solidification effect on the heavy metals, and the solidification efficiencies of zinc, copper, cadmium, chromium, lead, and arsenic were 81.9%, 90.0%, 93.5%, 91.8%, 99.6% and 95.5%, respectively. Additionally, the solidification efficiency of PCDD/Fs was 56.5%. The heavy metals and PCDD/Fs in MSWI FA solidified by physical adsorption, wrapping and chemical precipitation. The continuous calcium carbonate structure adsorbed and encased the MSWI FA, and the heavy metals in the MSWI FA were converted from a free state to carbonate precipitates through carbonation, and the carbonate precipitate was more likely to be physical solidification by calcium carbonate.

15.
J Cutan Pathol ; 2021 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-34622970

RESUMO

Primary cutaneous anaplastic large-cell lymphoma (pC-ALCL) is distinguished from systemic anaplastic large-cell lymphoma (S-ALCL) with cutaneous involvement. Although pC-ALCL is a unique entity with different genetics, clinical characteristics, and prognosis, its causes are unknown. Herein, we report the case of a Chinese woman with a 4-month history of a gradually enlarged ulcerative mass in her right forearm following an unidentified insect bite. Biopsy revealed an extensive infiltrate with patches of large anaplastic lymphoid cells. These cells were immunohistochemically positive for CD45, CD30, and TIA-1 and negative for CD2, CD3, CD4, CD5, CD20, CD7, CD8, and ALK-1. DUSP22-IRF4 rearrangement was detected; on the other hand, TP63 rearrangement was not observed by fluorescence in situ hybridization (FISH). No Epstein-Barr virus-encoded small RNAs (EBERs) were detected by ISH. Rearrangement of monoclonal TCR gene was found using BIOMED-2 polymerase chain reaction. No abnormality was found on the subsequent positron emission tomography-computed tomography (PET-CT) scan. After five cycles of cyclophosphamide + doxorubicin + vincristine + prednisolone (CHOP) chemotherapy, the patient achieved complete remission. This is the first report of a unique pC-ALCL with DUSP22-IRF4 rearrangement following an insect bite other than S-ALCL involving the skin.

16.
Front Oncol ; 11: 725988, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34631555

RESUMO

Background: Liver metastases (LM) are the most common tumors encountered in the liver and continue to be a significant cause of morbidity and mortality. Identification of the primary tumor of any LM is crucial for the implementation of effective and tailored treatment approaches, which still represents a difficult problem in clinical practice. Methods: The resection or biopsy specimens and associated clinicopathologic data were archived from seven independent centers between January 2017 and December 2020. The primary tumor sites of liver tumors were verified through evaluation of available medical records, pathological and imaging information. The performance of a 90-gene expression assay for the determination of the site of tumor origin was assessed. Result: A total of 130 LM covering 15 tumor types and 16 primary liver tumor specimens that met all quality control criteria were analyzed by the 90-gene expression assay. Among 130 LM cases, tumors were most frequently located in the colorectum, ovary and breast. Overall, the analysis of the 90-gene signature showed 93.1% and 100% agreement rates with the reference diagnosis in LM and primary liver tumor, respectively. For the common primary tumor types, the concordance rate was 100%, 95.7%, 100%, 93.8%, 87.5% for classifying the LM from the ovary, colorectum, breast, neuroendocrine, and pancreas, respectively. Conclusion: The overall accuracy of 93.8% demonstrates encouraging performance of the 90-gene expression assay in identifying the primary sites of liver tumors. Future incorporation of the 90-gene expression assay in clinical diagnosis will aid oncologists in applying precise treatments, leading to improved care and outcomes for LM patients.

17.
Blood Adv ; 2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34592762

RESUMO

Multiple myeloma, a plasma cell malignancy in the bone marrow, remains largely incurable with currently available therapeutics. In this study, we discovered that the activated-leukocyte-cell-adhesion-molecule (ALCAM) interacted with epidermal growth factor receptor (EGFR), and regulated myelomagenesis. ALCAM was a negative regulator of myeloma clonogenicity. ALCAM expression was positively correlated with patients' survival. ALCAM-knockdown myeloma cells displayed enhanced colony formation in the presence of bone marrow stromal cells (BMSCs). BMSCs supported myeloma colony formation by secreted epidermal growth factor (EGF), which bound with its receptor (EGFR) on myeloma cells and activated Mek/Erk cell signaling, PI3K/Akt cell signaling and hedgehog pathway. ALCAM could also bind with EGFR, block EGF from binding to EGFR, and abolish EGFR-initiated cell signaling. Hence, our study identifies ALCAM as a novel negative regulator of myeloma pathogenesis.

18.
Onco Targets Ther ; 14: 4537-4544, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34465999

RESUMO

Undifferentiated small round cell sarcoma (USRCS) is a rare malignant tumor. No reports about USRCS of the postcricoid region of the hypopharynx are available, and its clinical features and treatment guidelines remain undefined. We report a case of USRCS of the postcricoid region of the hypopharynx with treatment of surgery and radiotherapy. A 50-year-old man presented with a 4.9 cm x 3.7 cm tumor in the postcricoid region of the hypopharynx. It was diagnosed as USRCS. The tumor showed small round cells and positive immunoexpression of CD56, Cyclin D1, TLE1 and CD99, but no rearrangement or fusion of EWSR1, SS18, CIC, and BCOR. The patient underwent radiotherapy after surgery, without signs of tumor progression and metastasis at the 9-month follow-up. In conclusion, USRCS of postcricoid region of hypopharyngeal is ultra-rare. To make diagnosis, pathological examination is necessary. Surgery followed by radiotherapy might offer an optional treatment for USCRS.

19.
Cancer Manag Res ; 13: 6731-6741, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34471386

RESUMO

Background: In the present study, we have tried to understand how the level of risk and survival probability changes over time for patients with classical Hodgkin's lymphoma by employing conditional survival and annual hazard as dynamic estimates of prognosis and survival. Methods: This retrospective study reviewed the clinical data of patients with newly diagnosed classical Hodgkin's lymphoma admitted to Peking University Cancer Hospital between January 1, 2008, and December 31, 2017. Conditional survival and annual hazard rate were defined as the survival probability and yearly event rate, respectively, assuming that patients have survived for a defined time. Results: A total of 384 patients were included (median age, 32 years; range, 6-77 years), of which 218 (56.8%) patients had early-stage disease. The median follow-up time was 41.3 months. The 5-year conditional overall survival (COS) rates remained favorable and showed an increase from 89% at treatment to 94% at year 5, while the 5-year conditional failure-free survival (CFFS) rate increased from 70% at treatment to 96% at year 5. The annual hazard of failure decreased from over 15% at diagnosis to less than 5% after 3 years. Early-stage patients had constantly lower annual estimates for hazard of death (range, 0-3.0%) and failure (range, 0-14.3%). However, the hazard of failure in advanced-stage patients decreased from 24.2% at diagnosis to below 8% after 3 years, whereas the hazard of death was always at relatively low levels. Patients with a high IPS risk score (≥3) had significantly lower COS and CFFS during the first 4 years. Patients who received the BEACOPP regimen had better 5-year COS and 5-year CFFS than those who received the ABVD regimen. Conclusion: The survival probability increased and hazard of failure decreased over time.

20.
Cell Death Discov ; 7(1): 230, 2021 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-34482379

RESUMO

Mesenchymal stem-cell-derived small extracellular vesicles (MSC-EVs), as a therapeutic agent, have shown great promise in the treatment of neurological diseases. To date, the neurorestorative effects and underlying mechanism of MSC-EVs in Alzheimer's disease (AD) are not well known. Herein, we aimed to investigate the action of MSC-EVs on the neuronal deficits in ß-amyloid protein (Aß)-stimulated hippocampal neurons, or AD cell (SHSY5Y cell lines) and animal (APPswe / PS1dE9 mice) models. In the present study, the cell and AD models received a single-dose of MSC-EVs, and were then assessed for behavioral deficits, pathological changes, intracellular calcium transients, neuronal morphology alterations, or electrophysiological variations. Additionally, the nuclear factor E2-related factor 2 (Nrf2, a key mediator of neuronal injury in AD) signaling pathway was probed by western blotting in vitro and in vivo models of AD. Our results showed that MSC-EVs therapy improved the cognitive impairments and reduced the hippocampal Aß aggregation and neuronal loss in AD mice. Markedly, EV treatment restored the calcium oscillations, dendritic spine alterations, action potential abnormalities, or mitochondrial changes in the hippocampus of AD models. Also, we found that the Nrf2 signaling pathway participated in the actions of MSC-EVs in the cell and animal models. Together, these data indicate that MS-EVs as promising nanotherapeutics for restoration of hippocampal neuronal morphology and function in APP / PS1 mice, further highlighting the clinical values of MSC-EVs in the treatment of AD.

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