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1.
Clin Neurol Neurosurg ; 213: 107119, 2022 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-34998160

RESUMO

OBJECTIVE: Myocardial dysfunction is a known complication in patients who experience severe stressful events, such as traumatic brain injuries (TBI). One common manifestation is Takotsubo Cardiomyopathy (TC) which can appear concomitantly in patients with haemorrhagic brain injuries. There is often a management dilemma when two conditions with conflicting treatment regimens arise in the same individual. Previous systematic review had highlighted the importance of accurate diagnosis but there is no algorithm to aid decision-making in an emergency trauma setting. A systematic review was performed with the aim of establishing a new algorithm to aid in the diagnosis and management of TC patients with concurrent TBI. METHODS: We performed a comprehensive search of Pubmed, google scholar, Embase and Cochrane databases using keywords 'traumatic brain injury' and 'head injury' associated with keywords of 'Takotsubo cardiomyopathy,' 'Tako-tsubo cardiomyopathy,' 'stress cardiomyopathy,' 'stunned myocardium,' 'transient-left-ventricular ballooning syndrome,' 'apical ballooning syndrome,' 'myocardial dysfunction' or 'heart failure'. Non traumatic brain injury, blunt cardiac injury or cardiac events from chest trauma were excluded. The search was done between 1st to 4th October 2020 and only articles published after the year 2000 in English were included. Articles were then analysed in-depth. No articles were excluded after analysis to remove reporting bias. RESULTS: A total of 11 case reports and 7 cohort studies were analysed, giving a total number of 382 patients, with 36% of the patients analysed presenting with subdural haematoma, 27% with subarachnoid haemorrhage and 5% with extradural haematoma. Of the patients who underwent surgical interventions for traumatic brain injuries, 75% survived. 9% of patients in total were reported to have an EF of less than 55% whereas 51% had an EF of equal to or more than 55%. TTE details were not reported in a total of 35% of patients. All case reports which had followed up on their patient's cardiac status with repeated echocardiography had demonstrated a resolution of cardiac function independent of cardiac intervention. DISCUSSION: Our analysis was limited by the fact that not all papers analysed had reported the parameters we required. However, based on our review, we conclude that most patients with TC demonstrate a resolution of cardiac function independent of cardiac interventions from as fast as a few hours to as long as 6-12 weeks. Therefore, despite high cardiac risks, if neurosurgical intervention is needed, it should be offered to improve the chance of survival as transient cardiomyopathy can be supported with inotropes. We have developed a new algorithm for management of cases of concurrent TBI and TC.

2.
Anal Chem ; 2022 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-35020360

RESUMO

Room-temperature ionic liquids (RTILs) emerged as ideal solvents, and bipyridine as one of the most used ligands have been widely employed in surface science, catalysis, and molecular electronics. Herein, in situ shell-isolated nanoparticle-enhanced Raman spectroscopy (SHINERS) and STM break junction (STM-BJ) technique has been employed to probe the electrochemical process of bipyridine at Au(111)/IL interfaces. It is interestingly found that these molecules undertake a redox process with a pair of well-defined reversible peaks in cyclic voltammograms (CVs). The spectroscopic evidence shows a radical cation generated with rising new Raman peaks related to parallel CC stretching of a positively charged pyridyl ring. Furthermore, these electrochemically charged bipyridine is also confirmed by electrochemical STM-BJ at the single-molecule level, which displays a binary conductance switch ratio of about 400% at the redox potentials. This present work offers a molecular-level insight into the pyridine-mediated reaction process and electron transport in RTILs.

3.
Org Lett ; 24(1): 158-163, 2022 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-34898224

RESUMO

Comprehensive analyses of the metabolite spectra of Aspergillus sp. EGF 15-0-3 under different culture conditions revealed the presence of unique environmental-induced metabolites exclusively from the rice medium. Subsequent target isolation afforded four unprecedented indole diketopiperazine-based hybrids with a pyrano[3',2':7,8]isochromeno[4,3-b]pyrazino[2,1-i]indole core (1 and 2) or a spiro[piperazine-2,2'-pyrano[3,4,5-de]chromene] scaffold (3 and 4). Putative biosynthetic pathways for 1-4, with Diels-Alder cycloadditions as key steps, were proposed. 1-4 exhibited selective cytotoxicities among several human cancer cells.

4.
Curr Med Imaging ; 2021 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-34872481

RESUMO

OBJECTIVE: To investigate the role of whole-brain volume computed tomography (CT) perfusion in assessing early ischemic cerebrovascular diseases. MATERIALS AND METHODS: Seventy-two patients with early ischemic cerebrovascular diseases who had undergone routine CT scan and 320-row volume CT whole-brain perfusion imaging within 8 h after admission were retrospectively enrolled in this one-center case-sectional study. The perfusion parameters of cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT), time to peak (TTP), and dynamic CT angiogram (4D-CTA) were obtained and analyzed. RESULTS: Among 72 patients, 29 cases with 37 cerebral ischemic lesions were found in plain CT scan, whereas 51 cases with 76 lesions were found in whole-brain CT perfusion, with 30.6% more patients being detected. The CBF value was significantly lower in the abnormal than normal corresponding perfusion area in the healthy hemisphere (P<0.05), while the MTT and TTP values were significantly higher in the abnormal than the normal corresponding area (P<0.05). 4D-CTA image suggested that 59 cases had different degrees of stenosis or occlusion, including 11 mild, 18 moderate, 21 severe, and 9 occlusive cases. Four-D-CTA imaging could detect significantly (P<0.05) more patients with abnormal perfusion in severe cerebral vascular stenosis or occlusion than those with no, mild or moderate stenosis (93.33% vs. 16.67%) (P<0.05). The stenosis of intracranial and carotid arteries was positively correlated with MTT and TTP values (P<0.05). CONCLUSION: Whole-brain volume CT angiography can comprehensively display early cerebral ischemic lesions, cerebral blood perfusion status, and cerebral vascular stenosis, providing valuable information for early detection of ischemic cerebral diseases and appropriate treatment planning.

5.
Preprint em Inglês | bioRxiv | ID: ppbiorxiv-474273

RESUMO

The Omicron variant of SARS-CoV-2 has rapidly become the dominant infective strain and the focus efforts against the ongoing COVID-19 pandemic. Here we report an extensive set of structures of the Omicron spike trimer by its own or in complex with ACE2 and an anti-Omicron antibody. These structures reveal that most Omicron mutations are located on the surface of the spike protein, which confer stronger ACE2 binding by nearly 10 folds but become inactive epitopes resistant to many therapeutic antibodies. Importantly, both RBD and the closed conformation of the Omicron spike trimer are thermodynamically unstable, with the melting temperature of the Omicron RBD decreased by as much as 7{degrees}C, making the spiker trimer prone to random open conformations. An unusual RBD-RBD interaction in the ACE2-spike complex unique to Omicron is observed to support the open conformation and ACE2 binding, serving the basis for the higher infectivity of Omicron. A broad-spectrum therapeutic antibody JMB2002, which has completed Phase 1 clinical trial, is found to interact with the same two RBDs to inhibit ACE2 binding, in a mode that is distinguished from all previous antibodies, thus providing the structural basis for the potent inhibition of Omicron by this antibody. Together with biochemical data, our structures provide crucial insights into higher infectivity, antibody evasion and inhibition of Omicron.

6.
BMC Gastroenterol ; 21(1): 490, 2021 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-34930143

RESUMO

BACKGROUND: To assess the association of HSD17B13 rs72613567:TA allelic variant with liver disease, we performed the current review and meta-analysis. METHODS: Seven studies were identified by a search of CNKI,CBM,MEDLINE, PubMed, EMBASE, and CENTRAL databases from inception to November 2021. Odds ratios (ORs) with 95% confidence interval (CI) were calculated using random effects model or fixed effects model based on the between-study heterogeneity. The Stata 14.0 software was employed for data analysis. RESULTS: Statistical analysis showed that the HSD17B13 rs72613567:TA allelic variant can decrease the risk of hepatocellular carcinoma(HCC) in nonalcoholic fatty liver disease (NAFLD) patients, alcoholic fatty liver disease (ALD) patients and viral hepatitis patients (TA vs T OR = 0.766, 95% CI = 0.682-0.860, P = 0.000; TATA + TAT vs TT OR = 0.755, 95% CI = 0.645-0.885, P = 0.001) or healthy controls(TA vs T OR = 0.649, 95% CI = 0.431-0.977, P = 0.038). Besides, the HSD17B13 rs72613567:TA allelic variant can also provide protection from nonalcoholic fatty liver disease (NAFLD) not only in entire population (TA vs T OR = 0.669, 95% CI = 0.524-0.856, P = 0.001) but also in healthy people (TA vs T OR = 0.600, 95% CI = 0.464-0.777, P = 0.000). No significant publication bias found in this airticle. CONCLUSION: The present findings suggest HSD17B13 rs72613567:TA allelic variant can reduce the risk of HCC and NAFLD in the entire population studied.


Assuntos
17-Hidroxiesteroide Desidrogenases/genética , Carcinoma Hepatocelular , Neoplasias Hepáticas , Hepatopatia Gordurosa não Alcoólica , Alelos , Carcinoma Hepatocelular/genética , Humanos , Neoplasias Hepáticas/genética , Hepatopatia Gordurosa não Alcoólica/genética , Razão de Chances
7.
Nanomaterials (Basel) ; 11(12)2021 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-34947710

RESUMO

We theoretically demonstrate an approach to generate the double narrow Fano resonances via diffraction coupling of magnetic plasmon (MP) resonances by embedding 3D metamaterials composed of vertical Au U-shaped split-ring resonators (VSRRs) array into a dielectric substrate. Our strategy offers a homogeneous background allowing strong coupling between the MP resonances of VSRRs and the two surface collective optical modes of a periodic array resulting from Wood anomaly, which leads to two narrow hybridized MP modes from the visible to near-infrared regions. In addition, the interaction effects in the VSRRs with various geometric parameters are also systematically studied. Owing to the narrow hybrid MP mode being highly sensitive to small changes in the surrounding media, the sensitivity and the figure of merit (FoM) of the embedded 3D metamaterials with fabrication feasibility were as high as 590 nm/RIU and 104, respectively, which holds practical applications in label-free biosensing, such as the detection of medical diagnoses and sport doping drugs.

8.
Front Plant Sci ; 12: 771806, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34899796

RESUMO

Plant apoplast serves as the frontier battlefield of plant defense in response to different types of pathogens. Many pathogenesis-related (PR) proteins are accumulated in apoplastic space during the onset of plant-pathogen interaction, where they act to suppress pathogen infection. In this study, we found the expression of Triticum aestivum lipid transfer protein 3 (TaLTP3) gene was unregulated during incompatible interaction mediated by leaf rust resistance genes Lr39/41 at the early infection stage. Stable transgenic wheat lines overexpressing TaLTP3 exhibited enhanced resistance to leaf rust pathogen Puccinia triticina. Transcriptome analysis revealed that overexpression of TaLTP3 specifically activated the transcription of pathogenesis-related protein 1a (TaPR1a) and multiple plant hormone pathways, including salicylic acid (SA), jasmonic acid (JA), and auxin, in response to the infection of the model bacterial pathogen Pseudomonas syringae pv. tomato DC3000. Further investigation indicated that TaLTP3 physically associated with wheat TaPR1a protein in the apoplast. Transgenic wheat lines overexpressing TaLTP3 and TaPR1a showed higher accumulations of reactive oxygen species (ROS) during plant defense responses. All these findings suggested that TaLTP3 is involved in wheat resistance against leaf rust pathogen infection and forming a TaLTP3-TaPR1a complex in apoplast against this pathogen, which provides new insights into the functional roles of PR proteins.

9.
Org Lett ; 2021 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-34965138

RESUMO

Two novel diterpenoids, one with a rearranged trans,trans-fused tricyclo[10.3.0.04,6]pentadecane framework (1) and the other with an unprecedented 15S configuration (2), were isolated from Euphorbia helioscopia. Their structures were elucidated by extensive analysis of HR-ESI-MS, NMR, quantum-chemical calculation, and X-ray crystallographic data. Biosynthetically, 1 has a unique "cyclopropane-shift-like" biogenesis involving an oxa-di-π-methane (ODPM) rearrangement, which inspired us to accomplish the biomimetic conversion of 3 to 1. Moreover, compound 1 displayed a potent immunosuppressive effect by inhibiting Kv1.3 voltage-gated channels.

10.
Front Oncol ; 11: 771431, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34926280

RESUMO

Objective: Parasellar meningiomas (PMs) represent a cohort of skull base tumors that are localized in the parasellar region. PMs tend to compress, encase, or even invade the cerebral arteries and their perforating branches. The surgical resection of PMs without damaging neurovascular structures is challenging. This study aimed to analyze functional outcomes in a series of patients who underwent surgery with individualized cerebral artery protection strategies based on preoperative imaging. Methods: A retrospective review was performed on a single surgeon's experience of the microsurgical removal of PMs in 163 patients between January 2012 and March 2020. Individualized approaches with a bidirectional dissection strategy were used. Cerebral artery invasion classification, neurological outcomes, MRC Scale for muscle strength, and Karnofsky performance scale were used to assess tumor vascular invasion, functional outcome, and patient quality-of-life outcomes, respectively. Results: Total resection (Simpson grade I or II) was achieved in 114 patients (69.9%) in our study. A total of 44.7% of patients had improved vision at consecutive follow-ups, 51.1% were stable, and 3.8% deteriorated. Improvements in cranial nerves III, IV, and VI were observed in 41.1%, 36.2%, and 44.8% of patients, respectively. The mean follow-up time was (38.8 ± 27.9) months, and the KPS at the last follow-up was 89.6 ± 8.5. Recurrence was observed in eight patients (13.8%) with cavernous sinus meningiomas, and the recurrence rates in anterior clinoid meningiomas and medial sphenoid wing meningiomas were 3.8% and 2.8%, respectively. Conclusions: Preoperative imaging is important in the selection of surgical approaches. Maximum tumor resection and cerebral artery protection can be achieved concurrently by utilizing the bidirectional dissection technique. Individualized cerebral artery protection strategies provide great utility in improving a patient's quality of life.

11.
Gene ; 813: 146095, 2021 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-34902509

RESUMO

The corpus allatum (CA) is an endocrine organ of insects that synthesizes juvenile hormone (JH). Yet little is known regarding the global gene expression profile for the CA, although JH signaling pathway has been well-studied in insects. Here, we report the availability of the transcriptome resource of the isolated CA from the final (fifth) instar larvae of the silkworm, Bombyx mori when the JH titer is low. We also compare it with prothoracic gland (PG) that produces the precursor of 20-hydroxyecdysone (20E), to find some common features in the JH and 20E related genes between the two organs. A total of 17,262 genes were generated using a combination of genome-guided assembly and annotation, in which 10,878 unigenes were enriched in 58 Gene Ontology terms, representing almost all expressed genes in the CA of the 5th instar larvae of B. mori. Transcriptome analysis confirmed that gene for Torso, the receptor of prothoracicotropic hormone (PTTH), is present in the PG but not in the CA. Transcriptome comparison and quantitative real time-PCR indicated that 11 genes related to JH biosynthesis and regulation and six genes for 20E are expressed in both the CA and PG, suggesting that the two organs may cross talk with each other through these genes. The temporal expression profiles of the two genes for the multifunctional neurohormonal factor sericotropin precursor and the uncharacterized protein LOC114249572, the most abundant in the CA and PG transcriptomes respectively, suggested that they might play important roles in the JH and 20E biosynthesis. The present work provides new insights into the CA and PG.

12.
Nat Commun ; 12(1): 6653, 2021 11 17.
Artigo em Inglês | MEDLINE | ID: mdl-34789768

RESUMO

BRCA1-BARD1 heterodimers act in multiple steps during homologous recombination (HR) to ensure the prompt repair of DNA double strand breaks. Dysfunction of the BRCA1 pathway enhances the therapeutic efficiency of poly-(ADP-ribose) polymerase inhibitors (PARPi) in cancers, but the molecular mechanisms underlying this sensitization to PARPi are not fully understood. Here, we show that cancer cell sensitivity to PARPi is promoted by the ring between ring fingers (RBR) protein RNF19A. We demonstrate that RNF19A suppresses HR by ubiquitinating BARD1, which leads to dissociation of BRCA1-BARD1 complex and exposure of a nuclear export sequence in BARD1 that is otherwise masked by BRCA1, resulting in the export of BARD1 to the cytoplasm. We provide evidence that high RNF19A expression in breast cancer compromises HR and increases sensitivity to PARPi. We propose that RNF19A modulates the cancer cell response to PARPi by negatively regulating the BRCA1-BARD1 complex and inhibiting HR-mediated DNA repair.

13.
Rapid Commun Mass Spectrom ; : e9219, 2021 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-34740284

RESUMO

RATIONALE: Panax ginseng (PG) and American ginseng (AMG) are both medicinal plants of the Panax genus in the Acanthopanax family. Although the chemical components of PG and AMG are similar, there are many differences of their bioactivities. In this study, the biochemical mechanisms of different bioactivities of PG and AMG were explored by researching the differential metabolites in plasma after administrations of PG and AMG, respectively. METHODS: In order to explore the material basis of differential bioactivities, two groups of mice were administrated orally with PG and AMG, and the method of metabonomics was used to identify the differential metabolites in the plasma. Then the network pharmacology based on the differential metabolites was processed. Afterward, the metabolite-target-pathway network of PG and AMG was constructed, thus the pathways related to different bioactivities were analyzed. RESULTS: Through the analysis of PCA and OPLS-DA, there were 10 differential metabolites identified in the PG group, and 8 differential metabolites identified in the AMG group. Based on the network pharmacology, the differential metabolites were classified and related to differential bioactivities of PG and AMG. In the PG group, there were 6 metabolites related to the effects of aphrodisiac and exiting the nerve, and 5 metabolites associated to raise blood pressure. In the AMG group, 5 metabolites were classified to the effect of inhibiting the nerve center, and 6 metabolites were related to antihypertensive. CONCLUSIONS: This study explored the material basis of the differential biological activity between PG and AMG, which was significantly to research PG and AMG used and promote human health.

14.
Cancers (Basel) ; 13(21)2021 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-34771553

RESUMO

Myelodysplastic syndromes (MDSs) are heterogeneous for their morphology, clinical characteristics, survival of patients, and evolution to acute myeloid leukemia. Different prognostic scoring systems including the International Prognostic Scoring System (IPSS), the Revised IPSS, the WHO Typed Prognostic Scoring System, and the Lower-Risk Prognostic Scoring System have been introduced for categorizing the highly variable clinical outcomes. However, not considered by current MDS prognosis classification systems, gene variants have been identified for their contribution to the clinical heterogeneity of the disease and their impact on the prognosis. Notably, TP53 mutation is independently associated with a higher risk category, resistance to conventional therapies, rapid transformation to leukemia, and a poor outcome. Herein, we discuss the features of monoallelic and biallelic TP53 mutations within MDS, their corresponding carcinogenic mechanisms, their predictive value in current standard treatments including hypomethylating agents, allogeneic hematopoietic stem cell transplantation, and lenalidomide, together with the latest progress in TP53-targeted therapy strategies, especially MDS clinical trial data.

15.
Materials (Basel) ; 14(21)2021 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-34771958

RESUMO

It has become one of the research directions of intelligent materials for self-healing asphalt pavements to use a bionic microvascular containing oily rejuvenator. The rejuvenator in a microvascular can carry out the healing of asphalt micro-cracks, thus reducing the damage to and prolonging the life of asphalt pavement. The aim of this work was to investigate the smart self-healing capability of an asphalt/microvascular material through its microstructure and mechanical properties. Microstructure observation indicated no interface separation between the microvasculars and bitumen matrix. Micro-CT images showed that microvasculars dispersed in asphalt samples without accumulation or tangles. The phenomenon of microcracks healing without intervention was observed, which proved that the fractured asphalt sample carried out the self-healing process with the help of rejuvenator diffusing out from the broken microvasculars. The self-healing efficiency of asphalt samples was also evaluated through a tensile test considering the factors of microvasculars content, healing time and healing temperature. It was found that the tensile strength of the asphalt samples was greatly enhanced by the addition of microvasculars under a set test condition. Self-healing efficiency was enhanced with more broken microvasculars in the rupture interface of the asphalt sample. During two self-healing cycles, the self-healing efficiency of the asphalt sample with three microvascular per 1 cm2 of a broken interface were able to reach 80% and 86%. This proves that microvasculars containing rejuvenator play a practical role in the self-healing process of asphalt. With an increase in temperature from 0 to 30 °C, the self-healing capability of the asphalt samples increased dramatically. An increase in time increased the self-healing capability of the bitumen samples. At last, a preliminary mathematical model also deduced that the self-healing efficiency was determined by the individual healing steps, including release, penetration and diffusion of the rejuvenator agent.

16.
Environ Technol ; : 1-12, 2021 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-34758705

RESUMO

The removal of unsymmetrical dimethylhydrazine (UDMH) has long been a concern because of its harmful effect on the environment and humans. This study aimed to prepare a novel graphene oxide/O-carboxymethyl chitosan (GO/CMC) composite adsorbent using the solution-blending method for the removal of UDMH from wastewater. The prepared GO/CMC was systematically characterized by Fourier-transform infrared, Raman, scanning electronic microscopy, transmission electron microscopy, thermogravimetric, and zeta potential analyses. The effects of initial pH, temperature, adsorbent dosage, initial concentration, contact time, and recyclability on the UDMH adsorption behaviour of GO/CMC were studied. The adsorption kinetics was consistent with the pseudo-second-order kinetics model, and the adsorption process was mainly controlled by chemisorption. Adsorption isotherms indicated that the adsorption of UDMH by GO/CMC followed the Langmuir adsorption isotherm. The adsorption mechanisms were mainly electrostatic attraction, hydrogen bonding, and surface complexation. Furthermore, GO/CMC composites can be used as a renewable and eco-friendly adsorbent for the removal of UDMH wastewater. The designed GO/CMC composites exhibited a relatively satisfactory recyclability and removal efficiency after five adsorption-desorption cycles.

17.
Transfusion ; 2021 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-34813663

RESUMO

BACKGROUND: Cold agglutinin disease (CAD) is a rare autoimmune hemolytic anemia mediated by immunoglobulin M autoantibodies that bind to the "I" antigen on erythrocytes. IgM binding results in either agglutination at ≤37°C, activation of the classical complement pathway, or both. Patients with CAD can have transient agglutination-mediated circulatory symptoms triggered by exposure to cold conditions. Separately, patients with CAD can experience complement-mediated symptoms such as anemia, hemolysis, and fatigue, but the effect of the season on these complement-mediated manifestations of CAD and clinical outcomes is not well understood. METHODS: Using data from the Optum® de-identified Electronic Health Record dataset, we compared hemoglobin, markers of hemolysis (bilirubin and lactate dehydrogenase [LDH]), and healthcare resource utilization (HRU) between seasons for 594 patients (62% female; 66% aged ≥65 years) with CAD (defined as having CAD-related terms in their clinical notes on ≥3 separate occasions between December 2008 and May 2016). Laboratory parameters and HRU were compared between seasons using multivariate regression models. RESULTS: Estimated median hemoglobin (9.87 g/dL in summer and 9.86 g/dL in winter; P = 0.944) and bilirubin (1.04 mg/dL in summer and 1.09 mg/dL in winter; P = 0.257) were similar in winter versus summer. While LDH was statistically significantly higher in winter compared with summer (P < 0.001), the estimated median value was above normal for both seasons (309 U/L in summer and 367 U/L in winter). HRU measures and transfusion and thromboembolism rates were similar across seasons. CONCLUSIONS: Patients with CAD had evidence of persistent chronic hemolysis, HRU, and thromboembolism risk year round.

18.
Front Oncol ; 11: 660487, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34722234

RESUMO

Objective: Complete resection of jugular foramen tumors with minimal cranial nerve complications remains challenging even for skilled neurosurgeons. Here, we introduce a modified paracondylar approach, named the suboccipital paracondylar-lateral cervical (SPCLC) approach for this purpose. We also share the follow-up data of our series and discuss the advantages and limitations of this modified paracondylar approach. Methods: We included 64 patients with jugular foramen tumors who underwent surgery by the same senior neurosurgeon between November 2011 and August 2020. All patients were treated with the SPCLC approach, which aimed for gross total tumor removal in a single-stage operation. The clinical characteristics, including preoperative and postoperative neurological status, the extent of surgical resection, and follow-up data were retrospectively acquired and evaluated. Results: There were 48 schwannomas, nine meningiomas, three paragangliomas, one hemangiopericytoma, one chordoma, one endolymphatic sac tumor, and one Langerhans' cell histiocytosis. The median age of our patients was 43 years (range: 21-77 years). Dysphagia, hoarseness, and tongue deviation were observed in 36, 26, and 28 patients, respectively. Thirty-two patients had hearing function impairments, including hearing loss or tinnitus. Gross total resection was achieved in 59 patients (59/64, 92.2%). Gamma Knife treatment was used to manage residual tumors in five patients. Postoperatively, new-onset or aggravative dysphagia and hoarseness occurred in 26 and 18 cases, respectively. Nine patients developed new-onset facial palsy, and one patient developed new-onset hearing loss. There were no cases of intracranial hematoma, re-operation, tracheostomy, or death. At the latest follow-up, hearing loss and tinnitus had improved in 20 cases (20/32, 62.5%), dysphagia alleviated in 20 cases (20/36, 55.6%), and hoarseness improved in 14 cases (14/26, 53.8%). Over a mean follow-up period of 27.8 ± 19.5 months (range: 3-68 months), tumor recurrence was observed in one patient. Conclusion: The SPCLC approach, modified from the paracondylar approach, and was less invasive, safe, and efficient for certain jugular foramen tumors. Taking advantage of the anatomic understanding, clear operational vision, and appropriate surgical skills, it is possible to achieve gross total tumor removal and the preservation of neurological function.

19.
Front Oncol ; 11: 733680, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34722278

RESUMO

Hepatocellular carcinoma (HCC) is a common malignancy worldwide. Alpha-fetoprotein (AFP) is still the only serum biomarker widely used in clinical settings. However, approximately 40% of HCC patients exhibit normal AFP levels, including very early HCC and AFP-negative HCC; for these patients, serum AFP is not applicable as a biomarker of early detection. Thus, there is an urgent need to identify novel biomarkers for patients for whom disease cannot be diagnosed early. In this study, we screened and identified novel proteins in AFP-negative HCC and evaluated the feasibility of using autoantibodies to those protein to predict hepatocarcinogenesis. First, we screened and identified differentially expressed proteins between AFP-negative HCC tissue and adjacent non-tumor liver tissue using SWATH-MS proteome technology. In total, 2,506 proteins were identified with a global false discovery rate of 1%, of which 592 proteins were expressed differentially with 175 upregulated and 417 downregulated (adjusted p-value <0.05, fold-change FC ≥1.5 or ≤0.67) between the tumor and matched benign samples, including 14-3-3 zeta protein. For further serological verification, autoantibodies against 14-3-3 zeta in serum were evaluated using enzyme-linked immunosorbent, Western blotting, and indirect immunofluorescence assays. Five serial serum samples from one patient with AFP-negative HCC showed anti-14-3-3 zeta autoantibody in sera 9 months before the diagnosis of HCC, which gradually increased with an increase in the size of the nodule. Based on these findings, we detected the prevalence of serum anti-14-3-3 zeta autoantibody in liver cirrhosis (LC) patients, which is commonly considered a premalignant liver disease of HCC. We found that the prevalence of autoantibodies against 14-3-3 zeta protein was 16.1% (15/93) in LC patient sera, which was significantly higher than that in patients with chronic hepatitis (0/75, p = 0.000) and normal human sera (1/60, 1.7%, p = 0.01). Therefore, we suggest that anti-14-3-3 zeta autoantibody might be a biomarker for predicting hepatocarcinogenesis. Further follow-up and research of patients with positive autoantibodies will be continued to confirm the relationship between anti-14-3-3 zeta autoantibody and hepatocarcinogenesis.

20.
Cell Mol Immunol ; 18(11): 2541-2553, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34635806

RESUMO

Allogeneic hematopoietic cell transplantation (allo-HCT) is a promising therapeutic option for hematological malignancies, but relapse resulting predominantly from residual disease in the bone marrow (BM) remains the major cause of treatment failure. Using immunodeficient mice grafted with laboratory-generated human B-ALL, our previous study suggested that leukemia cells within the BM are resistant to graft-versus-leukemia (GVL) effects and that mobilization with CXCR4 antagonists may dislodge leukemia cells from the BM, enabling them to be destroyed by GVL effects. In this study, we extended this approach to patient-derived xenograft (PDX) and murine T-ALL and AML models to determine its clinical relevance and effects on GVHD and donor hematopoietic engraftment. We found that posttransplant treatment with the CXCR4 antagonist AMD3100 significantly improved the eradication of leukemia cells in the BM in PDX mice grafted with B-ALL cells from multiple patients. AMD3100 also significantly improved GVL effects in murine T-ALL and AML models and promoted donor hematopoietic engraftment in mice following nonmyeloablative allo-HCT. Furthermore, posttransplant treatment with AMD3100 had no detectable deleterious effect related to acute or chronic GVHD. These findings provide important preclinical data supporting the initiation of clinical trials exploring combination therapy with CXCR4 antagonists and allo-HCT.

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