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Objective To investigate the clinicopathological and prognostic characteristics of intestinal inflammatory myofibroblastic tumours(IMT)in middle-aged and elderly patients.Methods The clinical,pathologi-cal morphology,immunophenotype and follow-up results of 5 cases of intestinal IMT in middle-aged and elderly patients were retrospectively analyzed.Results 4 cases of IMT occurred in the right half colon and 1 in the ileum.Most patients(3/5)had a history of intestinal injury,starting the digestive tract symptoms and increased leukocytes.The tumor tissue was composed of fusiform myofibroblasts and fibroblasts arranged in storiform pattern,with an infiltrative growth pattern,accompanied by a large number of lymphocytes and plasma cells infiltration,collagen formation and myxedema.One case was atypically large and deformed.Immunophenotype:vimentin(5cases),SMA(5 cases),desmin(3 cases),ALK(3 cases),CK(2 cases)were positive.Caldesmon,CD34,β-catenin,MC,CD117,DOG1,S-100,BCL-2,CD99,CD68 were negative,and Ki-67 proliferation index was 1.28%to 10.01%.All the 5 cases underwent complete tumor resection and were followed up for 48.5 to 133 months.Among them,1 patient aged 83 was considered to have tumor recurrence 27 months after surgery.The other patient survived 122 months without tumor and died of other causes.All the others survived without tumor and were in good condition.Conclusion(1)Intestinal IMT in the middle-aged and elderly people in this group was more common in the right half colon,and most of them had a history of intestinal injury,first gastrointestinal symptoms and elevated white blood cells;(2)Vimentin and SMA were positive at the same time,and ALK was more positive;(3)4/5 patients had good surgical resection,and 1/5 patients could relapse 2~3 years after surgery;old age,ALK-positive,Ki67 up to 10%,atypia may be an important risk factor for intestinal IMT recurrence in the elderly,of which ALK-positive patients may have a recurrence risk of 1/3.
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Immunoassays are widely used in medicine, food, environment and other fields due to having the advantages of simpleness, rapidness and accuracy. Combining immunoassays with nanomaterials can improve the performance of immunoassays. Compared with traditional nanomaterials, upconversion nanoparticles (UCNPs) have excellent optical properties such as good photostability, long luminescence lifetime and narrow and tunable emission bands, which can significantly reduce background noise and improve analytical sensitivity when combined with immunoassay. This paper briefly introduces the luminescence mechanism of UCNPs, summarizes the synthesis and surface modification methods of UCNPs. And then 5 UCNPs-based immunoassay techniques, namely, fluorescence resonance energy transfer, inner filter effect, magnetic separation technique, upconversion-linked immunosorbent assay and upconversion immunochromatography, are discussed in detail. These sensing protocols of UCNPs-based immunoassays have been successfully utilized to detect various targets, including small molecules, macromolecules, and pathogens, all of which closely related to food safety, human health, and environmental pollution. Finally, the challenges and prospects of this technique are summarized and prospected. Although the UCNPs immunoassays based on antibodies and antigens have made great progress, most of the research is still in the stage of laboratory, and there is a long way to go to realize its social applications. There is a series of challenges need to be overcome. (1) Designing excellent water soluble and dispersive upconversion nanomaterials is needed. Hydrophilic ligands are bound to smaller upconversion nanoparticles and removing hydrophobic surface ligands are the most widely used methods to improve solubility and dispersity. (2) Multi-detection technology platforms and multi-mode simultaneous detection platforms have great potential, which will improve the efficiency of point of care detection. (3) The researchers also need to focus on some important problems. For examples, the upconversion luminescence efficiency of UCNPs is difficult to maintain, the synthesis method is complex, and the surface modification degree and functionalization are difficult to control.
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Checkpoint blockade revolutionized cancer therapy, but we still lack a quantitative, mechanistic understanding of how inhibitory receptors affect diverse signaling pathways. To address this issue, we developed and applied a fluorescent intracellular live multiplex signal transduction activity reporter (FILMSTAR) system to analyze PD-1-induced suppressive effects. These studies identified pathways triggered solely by TCR or requiring both TCR and CD28 inputs. Using presenting cells differing in PD-L1 and CD80 expression while displaying TCR ligands of distinct potency, we found that PD-1-mediated inhibition primarily targets TCR-linked signals in a manner highly sensitive to peptide ligand quality. These findings help resolve discrepancies in existing data about the site(s) of PD-1 inhibition in T cells while emphasizing the importance of neoantigen potency in controlling the effects of checkpoint therapy.
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Receptor de Muerte Celular Programada 1 , Transducción de Señal , Receptor de Muerte Celular Programada 1/metabolismo , Ligandos , Linfocitos T/metabolismo , Receptores de Antígenos de Linfocitos T/metabolismo , Antígeno B7-H1/metabolismoRESUMEN
Removal of phenolic pollutants from industrial wastewaters is always an important practical problem. Use of enzymes for dephenolization provides a green solution. In this work, enzymatic methods were developed by employing mushroom tyrosinase immobilized as enzyme-Cu3(PO4)2 hybrid nanoflowers and enzyme-metal organic framework (i.e., ZIF-8 and HKUST-1) hybrid composites, which were shown to be superior to processes mediated by tyrosinase immobilized on other supports in both dephenolization efficiency and reusability. Comparatively, tyrosinase@Cu3(PO4)2 and tyrosinase@HKUST-1 were better than tyrosinase@ZIF-8 in both specific activity and dephenolization efficiency. Typical phenolic pollutants, including 3 monophenols (phenol, p-cresol, p-chlorophenol) and 3 bisphenols (BPA, BPB, BPF), can be completely eliminated within 0.5-4 h. The dephenolization order was discussed based on the enzyme's substrate specificity. The operability and reusability of these hybrid biocomposites were highly improved by entrapping into alginate gels or by incorporating with modified magnetic Fe3O4 nanoparticles. Particularly, the magnetic biocatalyst was prepared via a facile one-pot/one-step de novo synthetic strategy, optimized by using response surface methodology (RSM). The as-prepared magnetic tyrosinase@mHKUST-1 retained a high dephenolization efficiency of 81% after 10 cycles and was effective for continuous dephenolization for at least 24 h. These hybrid biocomposites were also successfully applied to treatment of real industrial wastewater from a coke plant.
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Estructuras Metalorgánicas , Monofenol Monooxigenasa , Aguas Residuales , Fenoles , Cloruro de Sodio , Enzimas InmovilizadasRESUMEN
Objective: This overview of systematic reviews (SRs) and meta-analyses aims to critically appraise the methodology and reporting quality of relevant SRs and meta-analyses with the aim of identifying whether or not the use of valproate can prevent the switch to mania associated with antidepressant treatment in Chinese patients with depressive episodes. Methods: Electronic databases China National Knowledge Infrastructure (CNKI), Chinese Scientific Journal Database (VIP database) and Wanfang Database were searched for related SRs and meta-analyses from inception to the search date within Chinese restrictions. A total of 2 reviewers independently selected SRs and meta-analyses and collected related data, and a third reviewer was introduced if any disagreement occurred during the assessment. The Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) and the US Agency for Healthcare Research and Quality (AHRQ) were employed to evaluate quality of the reporting and methodology. Results: The switch rate in the sodium valproate group by 99% and was significantly lower than in the antidepressant-only group (0% vs 5.7%; OR = 0.18; 95% CI, 0.04-0.84; Z = 2.18; P = .03). The magnesium valproate group was similar to the sodium valproate group in switch rate; the switch rate in the antidepressant group was (2.2% vs 16.92%; OR = 0.11; 95% CI, 0.03-0.39; Z = 3.47; P = .0005). The switch rate in the salt valproate combined with a selective serotonin reuptake inhibitor (SSRI) group was lower than in the SSRI group (0.51% vs 8.4%; OR = 0.15; 95% CI, 0.04-0.51; Z = 3.01; P = .003). The switch rate in the valproate combined with serotonin noradrenaline reuptake inhibitor (SNRI) group was similar to the valproate combined with SNRI group (2.3% vs 17.5%; OR = 0.12; 95% CI, 0.03-0.53; Z = 2.79; P = .05). Conclusion: Salt valproate can reduce the switch rate related to antidepressant treatment in patients with depression.
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Antidepresivos , Inhibidores Selectivos de la Recaptación de Serotonina , Inhibidores de Captación de Serotonina y Norepinefrina , Ácido Valproico , Humanos , Antidepresivos/uso terapéutico , Pueblos del Este de Asia , Inhibidores Selectivos de la Recaptación de Serotonina/uso terapéutico , Inhibidores de Captación de Serotonina y Norepinefrina/uso terapéutico , Ácido Valproico/uso terapéutico , Sustitución de MedicamentosRESUMEN
Objective: To investigate the expression of MSI1 and HER2 in mammary Paget's disease, and the correlation between the expression levels of MSI1 and HER2 and the clinicopathologic characteristics and prognosis of the patients. Methods: Clinical data and paraffin-embedded specimens of 34 pairs of mammary Paget's disease and underlying breast cancer were collected at the Department of Pathology, Affiliated Lianyungang Oriental Hospital of Xuzhou Medical University from March 2011 to December 2019. Immunohistochemistry was used to detect the expression of MSI1 and HER2 in mammary Paget's disease and the accompanying breast cancer, and to analyze the correlation between the expression levels of MSI1 and HER2 and their clinicopathologic features, as well as their influence on prognosis. Results: In mammary Paget's disease, the positive rate of MSI1 was 91.2% (31/34) and the positive rate of HER2 was 88.2% (30/34); the expression of MSI1 and HER2 was positively correlated (P=0.001, r=0.530). The expression of MSI1 was positively correlated with menopausal status (r=0.372, P=0.030) and lymph node metastasis (r=0.450, P=0.008). HER2 expression was positively correlated with menopausal status (r=0.436, P=0.010), and negatively correlated with ER expression (r=-0.365, P=0.034). The co-expression of MSI1 and HER2 was positively correlated with age (r=0.347, P=0.044) and menopausal status (r=0.496, P=0.003), and negatively correlated with ER expression (r=-0.461, P=0.006). Conclusions: MSI1 and HER2 are highly expressed in mammary Paget's disease and their expression levels are positively correlated. The correlation analysis between clinicopathological features and prognosis suggests that both of them may be involved in the occurrence and development of mammary Paget's disease and are potential therapeutic targets for mammary Paget's disease.
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Humanos , Femenino , Enfermedad de Paget Mamaria/patología , Neoplasias de la Mama/patología , Pronóstico , Metástasis Linfática , Proteínas del Tejido Nervioso/metabolismo , Proteínas de Unión al ARNRESUMEN
OBJECTIVE@#To observe the effect of Tiaoqi Jieyu (regulating qi and relieving depression) acupuncture on the clinical symptoms of treatment-resistant depression (TRD), and to explore the relationship between the acupuncture pain sensitivity and symptom's improvement.@*METHODS@#A total of 78 patients with TRD were randomly divided into an observation group (39 cases, 3 cases dropped off) and a control group (39 cases, 4 cases dropped off). The patients in the control group were treated with medications according to the treatment plan of psychiatrists (at least one medication was 5-hydroxytryptamine reuptake inhibitor). On the basis of the control group, the patients in the observation group were treated with Tiaoqi Jieyu acupuncture, and Baihui (GV 20), Yintang (GV 24+), Yanglingquan (GB 34), Taichong (LR 3), Hegu (LI 4), Neiguan (PC 6), Yinlingquan (SP 9) and Zusanli (ST 36), etc. were selected. The acupuncture was given three times a week. Both groups were treated for 8 weeks. After 8-week treatment, the response rate of Hamilton depression scale-24 (HAMD-24) score after was evaluated in the two groups. The scores of HAMD-24 and Hamilton anxiety scale (HAMA) were compared between the two groups before treatment, after 4, 8-week treatment and 12 weeks after treatment (follow-up). After the first treatment and 8-week treatment, the visual analogue scale (VAS) score in the observation group was evaluated, and the correlation between VAS score after the first treatment and HAMD-24 score before treatment, between VAS score after the first treatment and the course of disease in the observation group was analyzed, and the correlation between difference of VAS after 8-week treatment and after the first treatment and difference of HAMD-24 score before treatment and after 8-week treatment was analyzed.@*RESULTS@#After 8-week treatment, the response rate of HAMD-24 score in the observation group was 52.8% (19/36), higher than 17.1% (6/35) in the control group (P<0.001). Compared before treatment, the scores of HAMD-24 and HAMA in the two groups were decreased after 4-week treatment, 8-week treatment and in follow-up (P<0.05), and those in the observation group were superior to the control group (P<0.05). After 8-week treatment, the acupuncture pain VAS score in the observation group was (5.28±2.13) points, which was higher than (3.33±1.62) points after the first treatment (P<0.001). There was a negative correlation between VAS score after the first treatment and HAMD-24 score before treatment in the observation group (r =-0.486, P=0.003); there was no correlation between acupuncture pain VAS score after the first treatment and the course of disease in the observation group (P>0.05). After 8-week treatment, there was a positive correlation between the difference of VAS score and the difference of HAMD-24 score in the observation group (r =0.514, P=0.001).@*CONCLUSION@#Tiaoqi Jieyu acupuncture could improve the depression and anxiety in patients with TRD, and the symptom's improvement is related to the recovery of acupuncture pain sensitivity.
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Humanos , Depresión/terapia , Resultado del Tratamiento , Terapia por Acupuntura , Puntos de Acupuntura , DolorRESUMEN
Objective: To explore the diagnosis, surgical management and outcome of jugular foramen chondrosarcoma (CSA). Methods: Fifteen patients with jugular foramen CSA hospitalized in the Department of Otorhinolaryngology Head and Neck Surgery of Chinese PLA General Hospital from December 2002 to February 2020 were retrospectively collected,of whom 2 were male and 13 were female, aging from 22 to 61 years old. The clinical symptoms and signs, imaging features, differential diagnosis, surgical approaches, function of facial nerve and cranial nerves IX to XII, and surgical outcomes were analyzed. Results: Patients with jugular foramen CSA mainly presented with facial paralysis, hearing loss, hoarseness, cough, tinnitus and local mass. Computed tomography (CT) and magnetic resonance (MR) could provide important information for diagnosis. CT showed irregular destruction on bone margin of the jugular foramen. MR demonstrated iso or hypointense on T1WI, hyperintense on T2WI and heterogeneous contrast-enhancement. Surgical approaches were chosen upon the sizes and scopes of the tumors. Inferior temporal fossa A approach was adopted in 12 cases, inferior temporal fossa B approach in 2 cases and mastoid combined parotid approach in 1 case. Five patients with facial nerve involved received great auricular nerve graft. The House Brackmann (H-B) grading scale was used to evaluate the facial nerve function. Preoperative facial nerve function ranked grade Ⅴ in 4 cases and grade Ⅵ in 1 case. Postoperative facial nerve function improved to grade Ⅲ in 2 cases and grade Ⅵ in 3 cases. Five patients presented with cranial nerves Ⅸ and Ⅹ palsies. Hoarseness and cough of 2 cases improved after operation, while the other 3 cases did not. All the patients were diagnosed CSA by histopathology and immunohistochemistry, with immunohistochemical staining showing vimentin and S-100 positive, but cytokeratin negative in tumor cells. All patients survived during 28 to 234 months' follow-up. Two patients suffered from tumor recurrence 7 years after surgery and received revision surgery. No complications such as cerebrospinal fluid leakage and intracranial infection occurred after operation. Conclusions: Jugular foramen CSA lacks characteristic symptoms or signs. Imaging is helpful to differential diagnosis. Surgery is the primary treatment of jugular foramen CSA. Patients with facial paralysis should receive surgery in time as to restore the facial nerve. Long-term follow-up is necessary after surgery in case of recurrence.
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Humanos , Masculino , Femenino , Adulto Joven , Adulto , Persona de Mediana Edad , Parálisis Facial/etiología , Diagnóstico Diferencial , Foramina Yugular , Estudios Retrospectivos , Tos , Ronquera , Recurrencia Local de Neoplasia , Condrosarcoma/cirugíaRESUMEN
OBJECTIVE@#To evaluate the feasibility and tolerability of metoprolol standard dosing pathway (MSDP) in Chinese patients with acute coronary syndrome (ACS).@*METHODS@#In this multicenter, prospective, open label, single-arm and interventional study that was conducted from February 2018 to April 2019 in fifteen Chinese hospitals. A total of 998 hospitalized patients aged ≥ 18 years and diagnosed with ACS were included. The MSDP was applied to all eligible ACS patients based on the standard treatment recommended by international guidelines. The primary endpoint was the percentage of patients achieving the target dose at discharge (V2). The secondary endpoints included the heart rate and blood pressure at V2 and four weeks after discharge (V4), and percentage of patients experiencing bradycardia (heart rate < 50 beats/min), hypotension (blood pressure < 90/60 mmHg) and transient cardiac dysfunction at V2 and V4.@*RESULTS@#Of the 998 patients, 29.46% of patients achieved the target dose (≥ 95 mg/d) at V2. The total population was divided into two groups: target group (patients achieving the target dose at V2) and non-target group (patients not achieving the target dose at V2). There was significant difference in the reduction of heart rate from baseline to discharge in the two groups (-4.97 ± 11.90 beats/min vs. -2.70 ± 9.47 beats/min, P = 0.034). There was no significant difference in the proportion of bradycardia that occurred in the two groups at V2 (0 vs. 0, P = 1.000) and V4 (0.81% vs. 0.33%, P = 0.715). There was no significant difference in the proportion of hypotension between the two groups at V2 (0.004% vs. 0.004%, P = 1.000) and V4 (0 vs. 0.005%, P = 0.560). No transient cardiac dysfunction occurred in two groups during the study. A total of five adverse events (1.70%) and one serious adverse event (0.34%) were related to the pathway in target group.@*CONCLUSIONS@#In Chinese ACS patients, the feasibility and tolerability of the MSDP have been proved to be acceptable.
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Objective: The objective of this study is to observe the effect of combination of lithium and lamotrigine in treatment of rapid-cycling bipolar disorder (RCBD). Method: We searched MEDLINE, EMBASE, Cochrane Library in English and CBM, CNKI, WANFANG, and CSSCI in Chinese to find literature from 1 January 2000 to 31 December 2020 related to the combination of lithium carbonate and lamotrigine for treatment of RCBD. Results: Five comparison studies with 265 subjects of 131 cases in a study group and 134 cases in a control group met the inclusion criteria and were included for the final meta-analysis. The comprehensive analysis shows that the study group had a significant lower score in mental symptoms than the control group (Z = 2.34, P = 0.02) with a random model (X 2 = 33.02, df = 7, P < 0.01). However, the differences were only shown in PANSS (Z = 5.18, P < 0.01) and BPRS (Z = 3.08, P < 0.01). There was no difference in response rate (54.9 vs. 45.7%; OR = 1.47; 95% CI: 0.79~2.73; Z = 1.21, P > 0.05,) and remission rate (47.9 vs. 45.9%; OR = 1.05; 95% CI: 0.49~2.25; Z = 0.13, P > 0.05,) found between the two groups. The response rate of lamotrigine and lithium combination was significantly higher compare to that of monotherapy of lithium in patients with no treatment resistant (82 vs. 54%; OR = 4.26; 95% CI: 1.65~10.99; Z = 3.99, P < 0.01) with the fixed effect model (X 2 = 0.89, df = 1, P > 0.05, I 2 = 0%). Conclusion: The combination of lithium and lamotrigine resulted in better improvement of psychotic symptoms and higher response rate in patients with RCBP with no treatment resistant.
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The immune checkpoint receptor lymphocyte activation gene 3 protein (LAG3) inhibits T cell function upon binding to major histocompatibility complex class II (MHC class II) or fibrinogen-like protein 1 (FGL1). Despite the emergence of LAG3 as a target for next-generation immunotherapies, we have little information describing the molecular structure of the LAG3 protein or how it engages cellular ligands. Here we determined the structures of human and murine LAG3 ectodomains, revealing a dimeric assembly mediated by Ig domain 2. Epitope mapping indicates that a potent LAG3 antagonist antibody blocks interactions with MHC class II and FGL1 by binding to a flexible 'loop 2' region in LAG3 domain 1. We also defined the LAG3-FGL1 interface by mapping mutations onto structures of LAG3 and FGL1 and established that FGL1 cross-linking induces the formation of higher-order LAG3 oligomers. These insights can guide LAG3-based drug development and implicate ligand-mediated LAG3 clustering as a mechanism for disrupting T cell activation.
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Antígenos CD/metabolismo , Activación de Linfocitos , Animales , Anticuerpos , Fibrinógeno , Antígenos de Histocompatibilidad Clase II/metabolismo , Humanos , Inmunoterapia , Ligandos , Ratones , Receptores Inmunológicos , Proteína del Gen 3 de Activación de LinfocitosRESUMEN
ABSTRACT: Aberrant expression of adenosine triphosphate-binding cassette subfamily C (ABCC), one of the largest superfamilies and transporter gene families of membrane proteins, is associated with various tumors. However, its relationship with liver hepatocellular carcinoma (LIHC) remains unclear.We used the Oncomine, UALCAN, Human Protein Atlas, GeneMANIA, GO, Kyoto Encyclopedia of Genes and Genomes (KEGG), TIMER, and Kaplan-Meier Plotter databases. On May 20, 2021, we searched these databases for the terms ABCC1, ABCC2, ABCC3, ABCC4, ABCC5, ABCC6, ABCC7, ABCC8, ABCC9, ABCC10, ABCC11, ABCC12, ABCC13, and "liver cancer." The exposure group comprised LIHC patients, and the control group comprised normal patients (those with noncancerous liver tissue). All patients shown in the retrieval language search were included. We compared the mRNA expression of these proteins in LIHC and control patients to examine the potential role of ABCC1-13 in LIHC.Relative to the normal liver tissue, mRNA expression of ABCC1/2/3/4/5/6/10 was significantly upregulated (Pâ<â.001), and that of ABCC9/11 significantly downregulated (both Pâ<â.001), in LIHC. ABCC mRNA expression varied with gender (Pâ<â.05), except for ABCC11-13; with tumor grade (Pâ<â0.05), except for ABCC7/12/13; with tumor stage (Pâ<â.05), except for ABCC11-13; and with lymph node metastasis status (Pâ<â.05), except for ABCC7/8/11/12/13. Based on KEGG enrichment analysis, these genes were associated with the following pathways: ABC transporters, Bile secretion, Antifolate resistance, and Peroxisome (Pâ<â.05). Except for ABCC12/13, the ABCCs were significantly associated with B cell, CD8+ T cell, CD4+ T cell, macrophage, neutrophil, and dendritic cell infiltration (Pâ<â.05). High mRNA expression of ABCC1/4/5/8 (Pâ<â.05) and low expression of ABCC6/7/9/12/13 (Pâ<â.05) indicated poor prognosis. Prognostic significance was indicated for ABCC2/13 for both men and women (Pâ<â.05); for ABCC1/6/12/13 for tumor grades 1-3 (Pâ<â.05); for ABCC5/11/12/13 for all tumor stages (Pâ<â.05); for ABCC1/11/12/13 for American Joint Committee on Cancer T stages 1-3 (Pâ<â.05); and for ABCC1/5/6/13 for vascular invasion. None showed prognostic significance for microvascular invasion (Pâ<â.05).We identified ABCC1/2/3/4/5/6/9/10/11 as potential diagnostic markers, and ABCC1/4/5/6/7/8/9/12/13 as prognostic markers, of LIHC. Our future work will promote the use of ABCCs in the diagnosis and treatment of LIHC.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Adenosina Trifosfato , Carcinoma Hepatocelular/genética , Biología Computacional , Femenino , Humanos , Neoplasias Hepáticas/genética , Masculino , PronósticoRESUMEN
The genetic basis of colorectal cancer (CRC) and its clinical associations remain poorly understood due to limited samples or targeted genes in current studies. Here, we perform ultradeep whole-exome sequencing on 1015 patients with CRC as part of the ChangKang Project. We identify 46 high-confident significantly mutated genes, 8 of which mutate in 14.9% of patients: LYST, DAPK1, CR2, KIF16B, NPIPB15, SYTL2, ZNF91, and KIAA0586. With an unsupervised clustering algorithm, we propose a subtyping strategy that classisfies CRC patients into four genomic subtypes with distinct clinical characteristics, including hypermutated, chromosome instability with high risk, chromosome instability with low risk, and genome stability. Analysis of immunogenicity uncover the association of immunogenicity reduction with genomic subtypes and poor prognosis in CRC. Moreover, we find that mitochondrial DNA copy number is an independent factor for predicting the survival outcome of CRCs. Overall, our results provide CRC-related molecular features for clinical practice and a valuable resource for translational research.
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Neoplasias Colorrectales , Exoma , Inestabilidad Cromosómica , Neoplasias Colorrectales/genética , Exoma/genética , Genómica , Humanos , Cinesinas , Secuenciación del Exoma/métodosRESUMEN
The cancer-testis antigen A-kinase anchor protein 3 (AKAP3) has been shown to have a strong association with breast cancer (BC). However, its role in BC progression received scant attention. We aimed to explore the prognostic implication of aberrant AKAP3 expression for a better knowledge of BC progression and improved treatment. AKAP3 expression was quantitated using tissue microarrays and immunohistochemistry (IHC). Cell viability, invasion, migration, apoptosis, and expressions of PTEN/PI3K/AKT/mTOR signaling components were assessed in AKAP3-overexpressed or si-AKAP3-transfected BC cells. Finally, elevated AKAP3 expression was observed in BC versus paracancerous tissues. BC patients with high AKAP3 expression showed a worse prognosis than low expression patients (P < 0.0001). AKAP3 overexpressions fueled cell growth, proliferation, migration, and invasion in HCC1937 and MDA-MB-468 BC cell lines, alongside increased expressions of PI3K/AKT/mTOR signaling components and PTEN suppression. These effects were pronouncedly reversed, together with elevated apoptosis, in cells transfected with si-AKAP3. Therefore, AKAP3 is upregulated in BC and promotes BC cell growth, invasion, and migration via PTEN/PI3K/AKT/mTOR signaling activation. It may serve as a prognosis indicator for BC survival.
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Proteínas de Anclaje a la Quinasa A , Neoplasias de la Mama , Proteínas Proto-Oncogénicas c-akt , Proteínas de Anclaje a la Quinasa A/genética , Proteínas de Anclaje a la Quinasa A/metabolismo , Apoptosis/genética , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Femenino , Humanos , Fosfohidrolasa PTEN/genética , Fosfohidrolasa PTEN/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Serina-Treonina Quinasas TOR/genética , Serina-Treonina Quinasas TOR/metabolismoRESUMEN
Post-acute sequelae of COVID-19 (PASC) represent an emerging global crisis. However, quantifiable risk factors for PASC and their biological associations are poorly resolved. We executed a deep multi-omic, longitudinal investigation of 309 COVID-19 patients from initial diagnosis to convalescence (2-3 months later), integrated with clinical data and patient-reported symptoms. We resolved four PASC-anticipating risk factors at the time of initial COVID-19 diagnosis: type 2 diabetes, SARS-CoV-2 RNAemia, Epstein-Barr virus viremia, and specific auto-antibodies. In patients with gastrointestinal PASC, SARS-CoV-2-specific and CMV-specific CD8+ T cells exhibited unique dynamics during recovery from COVID-19. Analysis of symptom-associated immunological signatures revealed coordinated immunity polarization into four endotypes, exhibiting divergent acute severity and PASC. We find that immunological associations between PASC factors diminish over time, leading to distinct convalescent immune states. Detectability of most PASC factors at COVID-19 diagnosis emphasizes the importance of early disease measurements for understanding emergent chronic conditions and suggests PASC treatment strategies.
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COVID-19/complicaciones , COVID-19/diagnóstico , Convalecencia , Inmunidad Adaptativa/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Autoanticuerpos/sangre , Biomarcadores/metabolismo , Proteínas Sanguíneas/metabolismo , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/metabolismo , COVID-19/inmunología , COVID-19/patología , COVID-19/virología , Progresión de la Enfermedad , Femenino , Humanos , Inmunidad Innata/genética , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Factores de Riesgo , SARS-CoV-2/aislamiento & purificación , Transcriptoma , Adulto Joven , Síndrome Post Agudo de COVID-19RESUMEN
BACKGROUND: Primary liver cancer (PLC) is a common cancer, and its morbidity and mortality are ranked 6th and 3rd in the world for malignant tumors, respectively. And this number is still on the rise, seriously endangering people's health. In recent years, acupuncture combined with Chinese herbal medicine have been widely used in the treatment of PLC, and there are few restrictions. However, we have not found a meta-analysis of their synergistic effects. Therefore, this systematic review and meta-analysis will evaluate the efficacy and acupuncture combined with Chinese herbal medicine in the treatment of primary liver cancer. METHOD: We will search the following databases from inception up to August 20, 2021: PubMed, Web of Science, Embase, AMED, Cochrane Library, CNKI, VIP, CBM, and Wanfang. There will be no restrictions regarding publication date or language. We will apply a combination of medical keywords and words, including "acupuncture," "Chinese herbal medicine" and "primary liver cancer". Additionally, we will manually search all reference lists from relevant systematic reviews to find other eligible studies. We will use the random effects model in REVMAN v5.3 for meta-analysis. The study for acupuncture combined with Chinese herbal medicine in the treatment of PLC was a randomized controlled study. Two researchers will independently review the research selection, data extraction, and research quality assessments. Finally, we will observe the outcome measures. RESULTS: This study will provide evidence-based medical evidence for the treatment of PLC with a combination of acupuncture and Chinese herbal medicine, and provide new ideas and methods for the treatment of PLC.Registration number: INPLASY202180103.
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Terapia por Acupuntura/métodos , Medicamentos Herbarios Chinos/uso terapéutico , Neoplasias Hepáticas/terapia , Terapia por Acupuntura/efectos adversos , Terapia Combinada , Medicamentos Herbarios Chinos/administración & dosificación , Medicamentos Herbarios Chinos/efectos adversos , Humanos , Neoplasias Hepáticas/mortalidad , Calidad de Vida , Ensayos Clínicos Controlados Aleatorios como Asunto , Proyectos de Investigación , Análisis de Supervivencia , Metaanálisis como AsuntoRESUMEN
BACKGROUNDA previous phase I study showed that the infusion of autologous Tregs expanded ex vivo into patients with recent-onset type 1 diabetes (T1D) had an excellent safety profile. However, the majority of the infused Tregs were undetectable in the peripheral blood 3 months postinfusion (Treg-T1D trial). Therefore, we conducted a phase I study (TILT trial) combining polyclonal Tregs and low-dose IL-2, shown to enhance Treg survival and expansion, and assessed the impact over time on Treg populations and other immune cells.METHODSPatients with T1D were treated with a single infusion of autologous polyclonal Tregs followed by one or two 5-day courses of recombinant human low-dose IL-2 (ld-IL-2). Flow cytometry, cytometry by time of flight, and 10x Genomics single-cell RNA-Seq were used to follow the distinct immune cell populations' phenotypes over time.RESULTSMultiparametric analysis revealed that the combination therapy led to an increase in the number of infused and endogenous Tregs but also resulted in a substantial increase from baseline in a subset of activated NK, mucosal associated invariant T, and clonal CD8+ T cell populations.CONCLUSIONThese data support the hypothesis that ld-IL-2 expands exogenously administered Tregs but also can expand cytotoxic cells. These results have important implications for the use of a combination of ld-IL-2 and Tregs for the treatment of autoimmune diseases with preexisting active immunity.TRIAL REGISTRATIONClinicalTrials.gov NCT01210664 (Treg-T1D trial), NCT02772679 (TILT trial).FUNDINGSean N. Parker Autoimmune Research Laboratory Fund, National Center for Research Resources.
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Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 1/terapia , Inmunoterapia Adoptiva , Interleucina-2/administración & dosificación , Linfocitos T Reguladores/trasplante , Adulto , Péptido C/sangre , Linfocitos T CD8-positivos , Supervivencia Celular , Terapia Combinada , Diabetes Mellitus Tipo 1/inmunología , Femenino , Hemoglobina Glucada/metabolismo , Humanos , Hipoglucemiantes/uso terapéutico , Insulina/uso terapéutico , Interleucina-2/efectos adversos , Recuento de Linfocitos , Masculino , Células T Asesinas Naturales , Proteínas Recombinantes/administración & dosificación , Factores de Tiempo , Transcriptoma , Adulto JovenRESUMEN
Biological processes have been widely used for the treatment of both domestic and industrial wastewaters. In such biological processes, pollutants are converted into pollution-free substances by microorganisms through oxidation-reduction reactions. Thus, how to quantify the internal oxidation-reduction properties wastewaters and seek out targeted countermeasures is essential to understand, operate, and optimize biological wastewater treatment systems. So far, no such approach is available yet. In this work, a novel concept of electron neutralization-based evaluation is proposed to describe the internal oxidation-reduction properties of wastewater. Pollutants in wastewater are defined as electron donor substances (EDSs) or electron acceptor substances (EASs), which could give or accept electrons, respectively. With such an electron neutralization concept, several parameters, i.e., electron residual concentration (R), economy-related index (E and Er), and economical evaluation index (Y and Yr), are defined. Then, these parameters are used to evaluate the performance and economic aspects of currently applied wastewater treatment processes and even optimize systems. Three case studies demonstrate that the proposed concept could be effectively used to reduce wastewater treatment costs, assess energy recovery, and evaluate process performance. Therefore, a new, simple, and reliable methodology is established to describe the oxidation-reduction properties of wastewater and assess the biological wastewater treatment processes.
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Fenómenos Biológicos , Contaminantes Químicos del Agua , Purificación del Agua , Electrones , Oxidación-Reducción , Eliminación de Residuos Líquidos , Aguas Residuales , Contaminantes Químicos del Agua/análisisRESUMEN
Objective: To discuss the techniques and repairing methods of various degree of compound tissue defects in the auriculotemporal region. Methods: Retrospective analysis was conducted on three cases of different repairing methods for huge compound tissue defects in different degrees in the auriculotemporal region after the resection of the malignant tumor or sinus tract due to repeated infection in our hospital. Results: Following total removal of the tumors or sinus tract in all patients, we applied retroauricular lingual flap transfer repairing, latissimus dorsi flap free transfer repairing and vascular anastomosis, scalp tissue expansion in stage Ⅰ, then repairing the lesion with expanded scalp and filling the huge mastoid cavity with abdominal fat in stage Ⅱ, respectively, according to the characteristics of compound tissue defects in the auriculotemporal region. All free flaps survived well. Conclusions: The anatomy of the auricular-temporal area is complex and involves important vascular and neural structures of head and neck and lateral skull base. The huge composite tissue defect following auriculotemporal region surgery, which is composed of skin, muscle and bone tissue, needs to be repaired in one stage. Therefore, flexible repairing methods should be chosen based on different situations, for attaining the goal of completely removing tumor and lesions, and then, covering the operation cavity.
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Humanos , Procedimientos de Cirugía Plástica , Estudios Retrospectivos , Trasplante de Piel , Lóbulo Temporal , Resultado del TratamientoRESUMEN
BACKGROUND@#Acupuncture therapy has shown promise for effectively relieving preoperative anxiety. Nevertheless, previous findings from randomized controlled trials (RCTs) are inconsistent and must be examined in detail.@*OBJECTIVE@#This study systematically evaluates the efficacy and safety of acupuncture therapy for preoperative anxiety as well as the quality of evidence supporting this application.@*SEARCH STRATEGY@#The China National Knowledge Infrastructure Database, Wanfang Data Journal Database, Chinese Biomedical Literature Database, Chongqing VIP, Embase, PubMed and Cochrane Library Databases were queried from their inception to 19, February 2020, using keywords such as "acupuncture therapy," "preoperative" and "anxioty." Manual searches expanded the search breadth and included conference abstracts and other reference lists.@*INCLUSION CRITERIA@#RCTs were included in the current study if they contained a comparison between a group of anxiety patients that received acupuncture therapy and a control group that received sham acupuncture.@*DATA EXTRACTION AND ANALYSIS@#Literature was reviewed, and various articles were selected using the NoteExpress 3.2.0 software. Two researchers independently screened and extracted data and evaluated the risk of bias in the included studies. The RevMan 5.3 software was used for data aggregation and the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) assessment was used to evaluate the quality of the study outcomes.@*RESULTS@#Twelve studies were included in the review, containing a total of 916 patients. Meta-analysis showed that, compared with the control group, patients who received acupuncture therapy had reduced State-Trait Anxiety Inventory Scale (STAI-S) score (mean difference [MD] = -9.07, 95% confidence interval [CI] [-13.19 to -4.96], P < 0.0001) and Visual Analogue Scale (VAS) score (MD = -1.37, 95% CI [-2.29 to -0.45], P = 0.003). However, for the Hamilton Anxiety Scale (HAMA) score, there was no difference between the two groups (MD = -3.98, 95% CI [-12.89 to 4.92], P = 0.38). Further, the GRADE assessment demonstrated that the STAI-S was of moderate quality, the VAS of low quality and the HAMA of very low quality.@*CONCLUSION@#Acupuncture therapy may be able to decrease anxiety in preoperative patients, but the results need to be further verified due to the small sample sizes and the low quality of evidence to date.