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1.
Methods Mol Biol ; 2371: 261-286, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34596853

RESUMO

Macrocyclic peptides represent promising scaffolds for targeting biomolecules with high affinity and selectivity, making methods for the diversification and functional selection of these macrocycles highly valuable for drug discovery purposes. We recently reported a novel phage display platform (called MOrPH-PhD) for the creation and functional exploration of combinatorial libraries of genetically encoded cyclic peptides. In this system, spontaneous, posttranslational peptide cyclization by means of a cysteine-reactive non-canonical amino acid is integrated with M13 bacteriophage display, enabling the creation of genetically encoded macrocyclic peptide libraries displayed on phage particles. Using this system, it is possible to rapidly generate and screen large libraries of phage-displayed macrocyclic peptides (up to 108 to 1010 members) in order to identify high-affinity binders of a target protein of interest. Herein, we describe step-by-step protocols for the production of MOrPH-PhD libraries, the screening of these libraries against an immobilized protein target, and the isolation and characterization of functional macrocyclic peptides from these genetically encoded libraries.

2.
Biosens Bioelectron ; 195: 113630, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34536724

RESUMO

Nitric oxide as a signal molecule participates in a variety of physiological and pathological processes but its real-time detection in cell assays still faces challenging because of the trace amount, short half-life and easy conversion to other substances. We report here a rational design by assembling highly π-conjugated and small capacitive gaphdiyne (GDY) with a coordination complex of hemin (HEM) into a molecularly assembled material of GDY/HEM to achieve ultrafast and real-time monitoring of nitric oxide in cell assays. GDY comprising alkynyl C atoms can hybridize with the HEM to enable strong π-π interaction and atomic dispersion of iron sites while avoiding the formation of catalytically inactive dimer for the HEM. These characteristics make the GDY/HEM an excellent sensing material towards nitric oxide, which has an ultrafast response time of 0.95 s, a low detection limit of 7 nM and long linear range up to 151.38 µΜ. The GDY/HEM realizes real-time monitoring nitric oxide released from cancer and normal cells, demonstrating its capability for cell analysis.


Assuntos
Técnicas Biossensoriais , Grafite , Hemina , Óxido Nítrico
3.
Mod Pathol ; 2021 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-34848831

RESUMO

The role of programmed cell death-ligand 1 (PD-L1) in cervical cancer has been widely investigated; however, the influences of other inhibitory B7 family members are poorly understood. We investigated the expression of PD-L1, B7 homolog 3 (B7-H3), B7-H4, and V-domain Ig suppressor of T-cell activation (VISTA) and their association with the clinicopathological features and outcomes of a large cohort of 673 patients with squamous cell carcinoma or adenocarcinoma of the uterine cervix. The positivity rates for PD-L1 (combined positive score ≥1), B7-H3 in tumor cells (TCs), B7-H4 (exclusively in TCs), VISTA in immune cells (ICs), and VISTA in TCs were 57.9%, 62.8%, 44.8%, 92.6%, and 4.8%, respectively, in 606 primary cervical cancer samples. Co-expression of PD-L1 with B7-H3 in TCs and with B7-H4 and VISTA in ICs was observed in 38.8%, 25.4%, and 57.9% of samples, respectively. B7-H3 in TCs and B7-H4 and VISTA in ICs were observed in 58.1%, 46.6%, and 83.1% of PD-L1-negative samples, respectively. These proteins were observed more frequently in squamous cell carcinomas and in moderately to poorly differentiated carcinomas. VISTA (in ICs) and B7-H4 were more frequent in primary tumors than in recurrent counterparts and correlated with improved survival; in contrast, B7-H3 positivity in TCs was less frequent in primary tumors and correlated with short disease-specific survival. Co-expression of B7-H4 and VISTA in ICs was an independent predictor of favorable outcomes overall and among patients with PD-L1-negative tumors. These data indicate that B7 family proteins exhibit differing expression patterns, distributions, and prognostic implications in cervical cancer. Furthermore, the co-expression of PD-L1 with other checkpoint proteins suggests that PD-1/PD-L1 blockade combined with modulating other immune checkpoints may present a novel therapeutic approach for cervical cancer. Future studies are needed to validate prognostic values of B7 family proteins and explore their biological roles in this malignancy.

4.
Electrophoresis ; 2021 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-34755364

RESUMO

A boron nitride nanosheet (BNNS)-assisted matrix solid-phase dispersion method was established to microextract alkaloids from medicinal plants. The target compounds were identified by high-performance liquid chromatography coupled with ultraviolet detection and ion mobility quadrupole time-of-flight mass spectrometry. During the experimental process, several important parameters, including the type of dispersant, the amount of dispersant, the grinding time, and the type of elution solvent, were optimized. Finally, the BNNSs were chosen as the best dispersant, and their microcosmic morphologies were identified by scanning electron microscopy and transmission electron microscopy. Because of the special property of BNNSs, the cost of this experiment was greatly reduced, especially in elution volume, sample amount (50 mg), and extraction time (2 min). Under the best conditions, 50 mg of sample powder was dispersed with 50 mg of BNNSs, the grinding time was 120 s, the mixed powder was eluted with 200 µL of methanol, and good linearity (r2  > 0.9993) and satisfactory recoveries (80-100%) were obtained. The inter- and intraday precisions were acceptable, with RSDs lower than 2.01 and 4.84%, respectively. The limits of detection ranged from 2.54 to 15.00 ng/mL, and the limits of quantitation were 8.47 to 50.00 ng/mL. The proposed method was successfully applied for the determination of liensinine, isoliensinine, and neferine in lotus plumule.

5.
J Nat Prod ; 2021 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-34846889

RESUMO

Overexpression of various pro-inflammatory factors in microglial cells tends to induce neurodegenerative diseases, for which there is no effective therapy available. Aureonitol (1) and seven analogues, including six previously undescribed [elatumenol A-F (2-4, 6-8, respectively)], along with two new orsellinic acid esters [elatumone A and B (9 and 10)], were isolated from Chaetomium elatum. The structures of the compounds were established through comprehensive analysis of spectroscopic data, including high-resolution mass spectra and one- and two-dimensional NMR, and absolute configurations determined by the Mosher method, dimolybdenum tetraacetate-induced circular dichroism, and theoretical calculations including electronic circular dichroism and NMR. Metabolites 3, 4, 7, and 8 exhibited antineuroinflammatory activity by attenuating the production of inflammatory mediators, such as nitric oxide, interleukin-6, interleukin-1ß, tumor necrosis factor-α, and reactive oxygen species. Western blot results indicated 8 decreases the level of inducible nitric oxide synthase and cyclooxygenase-2 and suppresses the expression of Toll-like receptor 4 and nuclear factor kappa-B (NF-κB) as well as the phosphorylation of the inhibitor of NF-κB and p38 mitogen-activated protein kinases in lipopolysaccharide-activated BV-2 microglial cells.

6.
J Pharm Biomed Anal ; 208: 114467, 2021 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-34775191

RESUMO

In this study, a supercritical fluid chromatography (SFC) method based on ion pair reagents was used to separate alkaloids. The chromatographic parameters, including the stationary phase, additive type, additive concentration, outlet pressure, temperature and flow rate, were optimized. Baseline separation was completed in 20 min on an Agilent Pursuit 5 PFP column (4.6 × 150 mm) using carbon dioxide as the mobile phase and 7.5 mM sodium 1-pentanesulfonate as an additive with gradient elution at 140 bar, 60 °C, and a flow rate of 1.5 mL/min. The retention rate and resolution of the analytes were satisfactory. The limits of detection were 27.04-298.03 ng/mL, and the limits of quantification were 90.15-993.42 ng/mL. The recoveries of low and high concentrations were 77.46-111.86% and 83.84-111.00%, respectively. This ion pair additive greatly improved the separation efficiency of alkaloids. Consequently, this SFC method was successfully applied to the separation of alkaloids from Rhizoma corydalis.

7.
Front Oncol ; 11: 749881, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34804936

RESUMO

Objective: To investigate the oncologic and reproductive outcomes of fertility-sparing treatments (FSTs) in atypical endometrial hyperplasia (AEH) and endometrial cancer (EC) patients with excess weight (EW). Methods: This retrospective study comprised patients with AEH or EC who achieved a complete response (CR) after FST from 2010 to 2018. The clinical characteristics, oncological and reproductive outcomes were compared between the excess weight (EW) group (body mass index (BMI)≥25 kg/m2) and normal weight (NW) group (BMI<25 kg/m2). The risk factors associated with recurrence and unsuccessful pregnancy in patients with EW were analyzed. Results: Overall, 227 patients were enrolled, including 139 (61.2%) in EW group and 88 (38.8%) in NW group. In patients with EW, the pregnancy rate, the live birth rate and the relapse rate were 29.8%, 23.4%, and 30.9%, respectively. In patients with NW, these rates were 61.1%, 47.2%, and 31.8%, respectively. No significant differences were observed in the time to remission (P=0.865) and disease-free survival (DFS) (P=0.750). Patients in NW group achieved a better pregnancy rate than patients in the EW group (P=0.034). The patients with EW using ovulation induction to increase fertility tended to have a shorter time to pregnancy (P=0.042). However, no significant risk factors associated with unsuccessful pregnancy were identified after the multivariate analysis. In terms of DFS, the combination of gonadotropin-releasing hormone agonist (GnRH-a) and LNG-IUD was better for patients with EW than GnRH-a or oral progestin therapy alone (P=0.044, adjusted hazard ratio (HR)=0.432, 95% confidence interval (CI): 0.152-1.229), especially for patients with EW diagnosed with EC (P=0.032). Conclusion: FSTs for overweight and obese patients should be more individualized. GnRH-a and/or LNG-IUD may be options prior to FSTs in patients with EW. Further prospective studies are needed.

8.
Front Vet Sci ; 8: 708077, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34805328

RESUMO

Dermatomycosis is the second major cause of morbidity in giant pandas (Ailuropoda melanoleuca), and seriously endangers its health. Previous observations indicated that the occurrence of dermatomycosis in the giant panda varies in different seasons. The skin microbiota is a complex ecosystem, but knowledge on the community structure and the pathogenic potentials of fungi on the skin of the giant panda remains limited. In this study, samples from the giant panda skin in different seasons were collected, and the mycobiota were profiled by 18S rRNA gene sequencing. In total, 375 genera in 38 phyla were detected, with Ascomycota, Basidiomycota, Streptophyta, and Chlorophyta as the predominant phyla and Trichosporon, Guehomyces, Davidiella, Chlorella, Asterotremella, and Klebsormidium as the predominant genera. The skin mycobiota of the giant panda changed in the seasons, and the diversity and abundance of the skin fungi were significantly higher in spring, autumn, and summer than in the winter. Several dermatomycosis-associated fungi were detected as opportunists in the skin mycobiota of healthy giant pandas. Clinical dermatomycosis in the giant panda is observed more in summer and autumn. In this study, the results indicated that the high diversity and abundance of the skin fungi may have enhanced the occurrence of dermatomycosis in autumn and summer, and that dermatomycosis-associated fungi are the normal components of the skin mycobiota.

9.
Curr Gene Ther ; 2021 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-34802404

RESUMO

BACKGROUND: Cancer, a malignant tumor, is caused by the failure of the mechanism that controls cell growth and proliferation. Late clinical symptoms often manifest as lumps, pain, ulcers, and bleeding. Systemic symptoms include weight loss, fatigue, and loss of appetite. It is a major disease that threatens human life and health. How to treat cancer is a long-standing problem that needs to be overcome in the history of medicine. METHOD: Traditional tumor treatment methods are poorly targeted, and the side effects of treatment seriously damage the physical and mental health of patients. In recent years, with the advancement of medical science and technology, the research on gene combined with mesenchymal stem cells to treat tumors has been intensified. Mesenchymal stem cells carry genes to target cancer cells, which can achieve better therapeutic effects. DISCUSSION: In the text, we systematically review the cancer treatment evolution from traditional methods to novel approaches that include immunotherapy, nanotherapy, stem cell theapy, and gene therapy. We provide the latest review of the application status, clinical trials and development prospects of mesenchymal stem cells and gene therapy for cancer, as well as their integration in cancer treatment. Mesenchymal stem cells are effective carriers carrying genes and provide new clinical ideas for tumor treatment. CONCLUSION: This review focuses on the current status, application prospects and challenges of mesenchymal stem cell combined gene therapy for cancer, and provides new ideas for clinical research.

10.
Opt Express ; 29(23): 37234-37244, 2021 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-34808800

RESUMO

Mid-infrared absorption spectroscopy is an effective method for detecting analyte fingerprints without labeling, but the inherent loss of metals in current methods is a main issue. Here, a sensing scheme was proposed that uses an all-dielectric grating metasurface and angular scanning of polarized light, and then it was verified by numerical simulation. The proposed fingerprint detection scheme could effectively couple a guided-mode resonance spectrum peak with the characteristic peak of the analyte's phonon-polariton in the mid-infrared region, significantly enhancing the interaction between light and the analyte. The novel scheme would realize broadband enhancement to detect a variety of substances, and facilitate mid-infrared sensing and analysis of trace substances.

11.
ACS Appl Mater Interfaces ; 13(46): 55102-55111, 2021 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-34762409

RESUMO

Although research progress on mimicking natural photosynthesis for solar-to-fuel conversion has been continuously made, exploring broadband spectral-responsive materials with suitable band positions and high stability still remains a huge challenge. Herein, we, for the first time, report novel AsP nanosheets (NSs) with P-type semiconducting property and enough negative conduction band, which can work as a stable near-infrared (NIR) region-responsive electron donor for water reductive hydrogen (H2) production. To mimic photosystem I, Au nanorods (NRs) act as electron transport media, which are also responsible for the enhanced electric field nearby, and 1T-MoS2 NSs as a hydrogen evolution catalyst are orderly coupled with AsP NSs with a sheet-rod-sheet structure by electrostatic self-assembly. The cascaded band level alignment enables unidirectional electron flow from AsP to Au and then to MoS2, and the optimum H2 production rate of the MoS2-Au-AsP ternary heterojunction reaches 125.52 µmol g-1 h-1 with good stability even after being stored for several months under light irradiation with a wavelength longer than 700 nm. This work provides a platform that is energetically tailored to drive a solar broad-spectrum fuel generation, including CO2 reduction and N2 fixation.

12.
Oncogene ; 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34782719

RESUMO

The molecular and cellular mechanisms underlying mammary tumour dormancy and cancer recurrence are unclear and remain to be elucidated. Here, we report that mammary epithelial-specific disruption of ß1 integrin in a murine model of Luminal B human breast cancer drastically impairs tumour growth with proliferation block, apoptosis induction and cellular senescence. ß1 integrin-deficient dormant lesions show activation of the tumour suppressor p53, and tumours that circumvent dormancy possess p53 mutation analogous to those in human disease. We further demonstrate that mammary epithelial deletion of p53 in ß1 integrin-deficient mice fully rescues tumour dormancy and bypasses cellular senescence. Additionally, recurrent ß1 integrin-deficient tumours exhibit fibrosis with increased cancer-associated fibroblast infiltration and extracellular matrix deposition, absent in fast-growing ß1 integrin/p53-deficient lesions. Taken together, these observations argue that ß1 integrin modulates p53-dependent cellular senescence resulting in tumour dormancy and that pro-tumourigenic stromal cues and intrinsic genetic mutation are required for dormancy exit.

13.
BMC Infect Dis ; 21(1): 1043, 2021 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-34625036

RESUMO

BACKGROUND: Current guidelines support different management of cryptococcosis between severely immunodeficient and immunocompetent populations. However, few studies have focused on cryptococcosis patients with mild-to-moderate immunodeficiency. We performed this study to determine the clinical features of pulmonary (PC) and extrapulmonary cryptococcosis (EPC) and compared them among populations with different immune statuses to support appropriate clinical management of this public health threat. METHODS: All cases were reported by 14 tertiary teaching hospitals in Jiangsu Province, China from January 2013 to December 2018. The trends in incidence, demographic data, medical history, clinical symptoms, laboratory test indicators, imaging characteristics and diagnostic method of these patients were then stratified by immune status, namely immunocompetent (IC, patients with no recognized underlying disease or those with an underlying disease that does not influence immunity, such as hypertension), mild-to-moderate immunodeficiency (MID, patients with diabetes mellitus, end-stage liver or kidney disease, autoimmune diseases treated with low-dose glucocorticoid therapy, and cancer treated with chemotherapy) and severe immunodeficiency (SID, patients with acquired immunodeficiency syndrome, haematologic malignancies, solid organ transplantation or haematologic stem cell transplantation, idiopathic CD4 lymphocytosis, agranulocytosis, aggressive glucocorticoid or immunosuppressive therapy and other conditions or treatments that result in severe immunosuppression). RESULTS: The clinical data of 255 cryptococcosis patients were collected. In total, 66.3% of patients (169) were IC, 16.9% (43) had MID, and 16.9% (43) had SID. 10.1% of the patients (17) with IC were EPC, 18.6% of the patients (8) with MID were EPC, and 74.4% of patients (32) were EPC (IC/MID vs. SID, p < 0.001). Fever was more common in the SID group than in the IC and MID groups (69.8% vs. 14.8% vs. 37.2%, p < 0.001). Of chest CT scan, most lesions were distributed under the pleura (72.7%), presenting as nodules/lumps (90.3%) or consolidations (10.7%). Pleural effusion was more common in SID group compared to IC group (33.3% vs. 2.4%, p < 0.001). Positivity rate on the serum capsular polysaccharide antigen detection (CrAg) test was higher in the SID group than in the other two groups [100.0% vs. 84.4% (MID) vs. 78.2% (IC), p = 0.013]. Positivity rate on the serum CrAg test was also higher in cryptococcal meningitis patients than in PC patients (100.0% vs. 79.5%, p = 0.015). CONCLUSIONS: The clinical presentation of MID patients is intermediate between SID and IC patients and is similar to that of IC patients. The serum CrAg test is more sensitive for the identification of SID or EPC patients.


Assuntos
Criptococose , Síndromes de Imunodeficiência , Pneumopatias , Meningite Criptocócica , China/epidemiologia , Criptococose/diagnóstico , Criptococose/epidemiologia , Humanos
14.
Sci Total Environ ; : 151026, 2021 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-34666096

RESUMO

Organic fertilizers may contain cadmium (Cd) and the transformation of organic materials in soil also has a role in soil-plant Cd distribution, both of which lead to Cd accumulation in plant edible parts. However, the advisability of applying organic fertilizer to remediate soils that are moderately and slightly contaminated with Cd has not been clarified. In this study, we investigated the impacts of an organic amendment (chicken manure) on the Cd concentration in rice grains (CdR) and the soil chemical properties over a five year period (10 rice seasons) within a slightly contaminated paddy soil in Hunan Province, subtropical China. We found that the CdR was reduced by 28%-56% as a result of the organic amendment. The within-year reduction in CdR was higher in late rice (43%-56%, averaging 51%) than in early rice (28%-45%, averaging 38%); however, the inter-annual reduction in CdR was fairly stable (40%-49%), which suggests that chicken manure amendment has a long-term and persistent remediation potential. The concentrations of DTPA-extractable Cd and exchangeable plus water-soluble Cd fractions in soil were reduced, whereas soil pH and the concentrations of soil organic C and its labile fractions increased. These results indicate a lower apparent phytoavailability of Cd in soil following organic amendment. A two-variable empirical model using DTPA-Cd extracted from the soil at the full heading stage of rice and a climatic factor (total precipitation during the rice growing season) showed great potential in effectively predicting CdR. Our study suggests that Cd phytoavailability in soil (indexed by DTPA-extractable and exchangeable Cd) and climatic factors (such as temperature and precipitation) may control inter-annual reductions in CdR following organic amendment in slightly contaminated paddy soils.

15.
Sensors (Basel) ; 21(19)2021 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-34640720

RESUMO

Localization based on scalar field map matching (e.g., using gravity anomaly, magnetic anomaly, topographics, or olfaction maps) is a potential solution for navigating in Global Navigation Satellite System (GNSS)-denied environments. In this paper, a scalable framework is presented for cooperatively localizing a group of agents based on map matching given a prior map modeling the scalar field. In order to satisfy the communication constraints, each agent in the group is assigned to different subgroups. A locally centralized cooperative localization method is performed in each subgroup to estimate the poses and covariances of all agents inside the subgroup. Each agent in the group, at the same time, could belong to multiple subgroups, which means multiple pose and covariance estimates from different subgroups exist for each agent. The improved pose estimate for each agent at each time step is then solved through an information fusion algorithm. The proposed algorithm is evaluated with two different types of scalar field based simulations. The simulation results show that the proposed algorithm is able to deal with large group sizes (e.g., 128 agents), achieve 10-m level localization performance with 180 km traveling distance, while under restrictive communication constraints.

16.
Dalton Trans ; 50(43): 15849-15854, 2021 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-34708848

RESUMO

Uniform lithium deposition is a benefit to achieving high-energy-density lithium metal batteries. There are many effective methods to suppress the dendritic growth of metallic lithium and promote the application of the lithium anode. However, the designation of lithiophilic sites at the atomic level remains a huge challenge. Herein, a two-dimensional porous conjugated porphyrin polymer linked by two acetylenic linkages from an in situ coupling reaction has been prepared on copper foil and employed as the lithiophilic host. The four electron-rich pyrrolic nitrogen atoms in the porphyrin building block and the linkage electron-rich sp-hybridized carbon atoms were regarded as precise lithiophilic sites, resulting in a decreased nucleation overpotential and dendrite free morphology. With uniform lithium deposition, the electrochemical performance of the electrode was significantly improved in regard to the overpotential, coulombic efficiency and lifespan. This work expands the precise construction of lithiophilic sites at the atomic level and benefits to further development of high-energy density lithium metal batteries.

17.
BMC Oral Health ; 21(1): 549, 2021 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-34702237

RESUMO

BACKGROUND: The purpose of the present study is to evaluate the prevalence of temporomandibular disorders (TMD) and their associated biological and psychological factors in Chinese university students. METHODS: A total of 754 students were included from Zunyi Medical University, each participant completed questionnaires and clinical examinations according to the Diagnostic Criteria for Temporomandibular Disorders. RESULTS: The overall prevalence of TMD was 31.7% among medical students. Subjects with TMD had a high prevalence of bruxism, empty chewing, unilateral chewing, chewing gum, anterior teeth overbite, anterior teeth overjet, depression, anxiety, and sleep disturbance. Moreover, sleep bruxism, empty chewing, unilateral chewing, anterior teeth overbite, depression, and anxiety were the strongest risk factors for TMD. CONCLUSIONS: Individuals with TMD have a high prevalence of psychological distress and oral parafunctional habits. Except for the psychological factors associated with TMD, bruxism, abnormal chewing, and malocclusion also shared similar risks for TMD.


Assuntos
Bruxismo , Bruxismo do Sono , Estudantes de Medicina , Transtornos da Articulação Temporomandibular , Bruxismo/complicações , Bruxismo/epidemiologia , China/epidemiologia , Humanos , Prevalência , Fatores de Risco , Transtornos da Articulação Temporomandibular/complicações , Transtornos da Articulação Temporomandibular/epidemiologia
18.
Lancet Oncol ; 22(11): 1609-1617, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34624252

RESUMO

BACKGROUND: Treatment options for patients with high-risk chemorefractory or relapsed gestational trophoblastic neoplasia are scarce. The synergistic antitumour effect of immunotherapy and antiangiogenic drugs has been shown in many solid tumours. This phase 2 trial evaluated the activity and safety of camrelizumab (PD-1 inhibitor) plus apatinib (VEGF receptor inhibitor) in patients with high-risk chemorefractory or relapsed gestational trophoblastic neoplasia. METHODS: This was a single-arm, open-label, phase 2 trial, done at a single tertiary health-care centre in Beijing, China. Women (18-70 years) with high-risk (International Federation of Gynecology and Obstetrics score ≥7) chemorefractory or relapsed gestational trophoblastic neoplasia who had received at least two lines of previously unsuccessful multidrug chemotherapy regimens and had an Eastern Cooperative Oncology Group performance status of 0-2 were eligible for inclusion. Patients received 4-week cycles of intravenous camrelizumab 200 mg every 2 weeks plus oral apatinib 250 mg once per day until disease progression or unacceptable toxicity. The primary endpoint was objective response rate assessed according to serum human chorionic gonadotrophin concentration. Activity and safety were analysed in all patients who received at least one dose of study drug. The study is ongoing, but recruitment is complete. The study is registered with ClinicalTrials.gov, NCT04047017. FINDINGS: Between Aug 7, 2019, and March 18, 2020, 20 patients enrolled; 19 (95%) were diagnosed with choriocarcinoma and one (5%) had placental site trophoblastic tumour. The median follow-up duration was 18·5 months (IQR 14·6-20·9). The objective response rate was 55% (95% CI 32-77); ten (50%; 95% CI 27-73) patients had complete response. The most common grade 3 treatment-related adverse events were hypertension (five [25%] patients), rash (four [20%] patients), neutropenia (two [10%]), leukocytopenia (two [10%]), and aspartate aminotransferase increase (two [10%]). One patient had a treatment-related serious adverse event (aspartate aminotransferase 19-times higher than the upper limit of normal). No grade 4 or 5 treatment-related adverse events were reported. INTERPRETATION: Camrelizumab plus apatinib showed promising antitumour activity and acceptable toxicity and could be a salvage therapy option for the treatment of high-risk chemorefractory or relapsed gestational trophoblastic neoplasia. Immune checkpoint inhibitors combined with chemotherapy for heavily-treated patients and upfront use of camrelizumab plus apatinib for patients with high-risk gestational trophoblastic neoplasia are under investigation in phase 2 trials. FUNDING: National Natural Science Foundation of China, Jiangsu Hengrui Pharmaceuticals.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doença Trofoblástica Gestacional/tratamento farmacológico , Piridinas/uso terapêutico , Adulto , Idoso , Inibidores da Angiogênese/uso terapêutico , China , Resistencia a Medicamentos Antineoplásicos , Feminino , Doença Trofoblástica Gestacional/mortalidade , Doença Trofoblástica Gestacional/patologia , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico , Pessoa de Meia-Idade , Gravidez , Recidiva , Resultado do Tratamento
19.
Front Oncol ; 11: 744256, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34671560

RESUMO

To generate robust patient-derived xenograft (PDX) models for epithelial ovarian cancer (EOC), analyze the resemblance of PDX models to the original tumors, and explore factors affecting engraftment rates, fresh cancer tissues from a consecutive cohort of 158 patients with EOC were collected to construct subcutaneous PDX models. Paired samples of original tumors and PDX tumors were compared at the genome, transcriptome, protein levels, and the platinum-based chemotherapy response was evaluated to ensure the reliability of the PDXs. Univariate and multivariate analyses were used to determine the factors affecting the engraftment rates. The engraftment success rate was 58.23% (92/158) over 3-6 months. The Ki-67 index and receiving neoadjuvant chemotherapy can affect the engraftment rate in primary patients. The PDX models generated in this study were found to retain the histomorphology, protein expression, and genetic alteration patterns of the original tumors, despite the transcriptomic differences observed. Clinically, the PDX models demonstrated a high degree of similarity with patients in terms of the chemotherapy response and could predict prognosis. Thus, the PDX model can be considered a promising and reliable preclinical tool for personalized and precise treatment.

20.
Micromachines (Basel) ; 12(10)2021 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-34683279

RESUMO

High precision-controlled movement of microscale devices is crucial to obtain advanced miniaturized motors. In this work, we report a high-speed rotating micromotor based on two-dimensional (2D) all-inorganic perovskite CsPbBr3 microplates controlled via alternating-current (AC) external electric field. Firstly, the device configuration with optimized electric field distribution has been determined via systematic physical simulation. Using this optimized biasing configuration, when an AC electric field is applied at the four-electrode system, the microplates suspended in the tetradecane solution rotate at a speed inversely proportional to AC frequency, with a maximum speed of 16.4 × 2π rad/s. Furthermore, the electrical conductivity of CsPbBr3 microplates has been determined in a contactless manner, which is approximately 10-9-10-8 S/m. Our work has extended the investigations on AC electric field-controlled micromotors from 1D to 2D scale, shedding new light on developing micromotors with new configuration.

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