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1.
Scand J Immunol ; : e13191, 2022 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-35538715

RESUMO

The present study focuses on the associations of serum immunoglobulin with disease activity, relapse/recurrence and renal involvement in Henoch-Schönlein purpura (HSP) children. 1683 Chinese children with HSP were recruited from January 2015 to January 2021. Laboratory data of blood samples and urine tests were collected. Renal biopsy was performed by the percutaneous technique. Patients' histories associated with HSP onset were obtained by interviews and questionnaires. (1) IgA and IgE were dramatically elevated in HSP patients as compared to their normal values and subject to a 1.75-3.09 fold and a 1.97-2.61 fold increase, respectively. (2) No significant correlation of the disease activity with IgA and IgE was determined, respectively. (3) The serum IgA levels were significantly lower in patients with relapse/recurrence than that in patients without relapse/recurrence, which may be attributed to the transmission of IgA-mediated immune complexes from blood to vessel walls. (4) No significant correlation was found between serum IgA, IgE levels and the pathological classification. HSP children have marked disorders of serum immunoglobulin profiles, characterized by significant increases in IgA and IgE. The detection of serum IgA may be applicable to predict relapse/recurrence of HSP whereas not associated with disease activity and renal involvement.

2.
Artigo em Inglês | MEDLINE | ID: mdl-35564422

RESUMO

Although children living in low- and middle-income countries (LMICs) account for 90% of the global population of children, depression, and anxiety among children in LMICs have been understudied. This study examines the prevalence of depression and anxiety and their associations with biological and psychosocial factors among children across China, with a focus on rural areas. We conducted a large-scale epidemiological study of depression and anxiety among 53,421 elementary and junior high school-aged children across China. The results show that 20% are at risk for depression, 6% are at risk for generalized anxiety, and 68% are at risk for at least one type of anxiety. Girls and junior high school students show a higher risk for both depression and anxiety symptoms, while socioeconomic status has varying associations to depression and anxiety symptoms. Our results also show consistent correlations between depression and anxiety symptoms and standard math test scores. These findings underscore the importance of identification, prevention, and treatment of youth depression and anxiety in underdeveloped areas. As China constitutes 15% of the global population of children under age 18, this study offers valuable information to the field of global mental health.

3.
Artigo em Inglês | MEDLINE | ID: mdl-35529930

RESUMO

This study aimed to evaluate the efficacy of nourishing Yin and clearing heat therapy (NYCH therapy) based on traditional Chinese medicine (TCM) in the treatment of radiotherapy-induced oral mucositis (RTOM) in nasopharyngeal carcinomas (NPCs). A total of eight online databases were searched from inception to September 2021 for randomized controlled trials (RCTs). The control group was treated with Western medicine (WM) alone, whereas the experimental group was treated with a combined NYCH and WM therapy. A total of 30 RCTs involving 2562 participants were ultimately included. NYCH therapy combined with conventional WM delayed the onset time (days) of RTOM (MD = 10.80, p < 0.001), and at that time, a higher cumulative radiotherapy dose (Gy) (MD = 5.72, p < 0.001) was completed in the experimental group. The combination regimen also reduced the incidence of severe oral mucositis (Grade III-IV) (RR = 0.25, p < 0.001). In addition, the treatment efficacy of the experimental group was significantly better than that of the control group (RR = 1.31, p < 0.001). Compared with the patients in the control group, the experimental group had lower xerostomia scores (MD = -1.07, p < 0.001) and more saliva (MD = 0.36, p < 0.001). NYCH combined with WM improved the efficacy of treating RTOM in NPC. This study provides a sufficient basis for conducting further large RCTs to prove the efficacy of NYCH.

4.
AAPS PharmSciTech ; 23(5): 141, 2022 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-35538376

RESUMO

Due to poor solubility and stability in acid conditions, the gastrointestinal administration of stiripentol (STP) is still a significant challenge. This study aimed to explore the applicability of effervescent tablets compressed from STP-loaded enteric solid dispersions to improve the solubility and stability of the insoluble and acid-labile drug. STP-loaded solid dispersions (STP-SDs) and the effervescent tablets (STP-SD-ETs) were prepared using solvent evaporation and dry granulation technology, respectively, and their formulations were optimized. Then, STP-SDs were characterized regarding solid state, in vitro release, stability, etc. Results showed that enteric amorphous STP-SDs were successfully prepared and significantly improved the solubility and stability of STP. Moreover, compared with STP suspensions, the bioavailability of STP-SD-ETs was as high as 138.71%. Concomitantly, STP-SD-ETs significantly increased the intestinal absorption rate of STP. Overall, the oral preparation encompassing enteric solid dispersion combined with effervescent tablet technology possesses excellent performance in enhancing dissolution, anti-acid hydrolysis stability, and absorption of STP. Our work provides a promising method to improve the delivery of drugs with poor solubility and acid-labile stability.


Assuntos
Dioxolanos , Disponibilidade Biológica , Solubilidade , Comprimidos
5.
Cell Death Dis ; 13(5): 434, 2022 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-35508480

RESUMO

As a critical member of the ubiquitin-specific proteolytic enzyme family, ubiquitin-specific peptidase 20 (USP20) regulates the stability of proteins via multiple signaling pathways. In addition, USP20 upregulation is associated with various cellular biological processes, such as cell cycle progression, proliferation, migration, and invasion. Emerging studies have revealed the pivotal role of USP20 in the tumorigenesis of various cancer types, such as breast cancer, colon cancer, lung cancer, gastric cancer and adult T cell leukemia. In our review, we highlight the different mechanisms of USP20 in various tumor types and demonstrate that USP20 regulates the stability of multiple proteins. Therefore, regulating the activity of USP20 is a novel tumor treatment. However, the clinical significance of USP20 in cancer treatment merits more evidence. Finally, different prospects exist for the continued research focus of USP20.


Assuntos
Neoplasias da Mama , Ubiquitina Tiolesterase , Transformação Celular Neoplásica , Feminino , Humanos , Ubiquitina Tiolesterase/genética , Ubiquitina Tiolesterase/metabolismo , Proteases Específicas de Ubiquitina/genética , Proteases Específicas de Ubiquitina/metabolismo , Ubiquitinação
6.
Org Lett ; 24(14): 2655-2659, 2022 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-35377668

RESUMO

Copper catalyzed regioselective and stereospecific coupling between aziridines and in situ generated pyridine Grignard reagents is reported. This method provides ß-pyridylethylamines with diverse structures and functionalities from aziridines and iodopyridines. ß-Pyridylethylamines are potential scaffolds for the synthesis of biologically active compounds often found in pharmaceuticals. The synthesis of challenging chiral dihydroazaindoles was also achieved through mild one-pot reaction conditions via aziridine opening followed by nucleophilic cyclization.


Assuntos
Aziridinas , Cobre , Aziridinas/química , Catálise , Cobre/química , Estrutura Molecular , Estereoisomerismo
7.
Chin J Nat Med ; 20(3): 161-176, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35369960

RESUMO

Simiao Wan (SMW) is a traditional Chinese formula, including Atractylodis Rhizoma, Achyranthis Bidentatae Radix, Phellodendri Chinensis Cortex and Coicis Semen at the ratio of 1:1:2:2. It can be used to the treatment of diabetes. However, its bioactive compounds and underlying mechanism are unclear. This study aimed to screen the antilipolytic fraction from SMW and investigate its therapeutic mechanisms on hepatic insulin resistance. Different fractions of SMW were prepared by membrane separation combined with macroporous resin and their antilipolytic activities were screened in fasted mice. The effects of 60% ethanol elution (ESMW) on lipolysis were investigated in 3T3-L1 adipocytes stimulated by palmitic acid (PA) and high fat diet (HFD)-fed mice. In our study, ESMW is the bioactive fraction responsible for the antilipolytic activity of SMW and 13 compounds were characterized from ESMW by UHPLC-QTOF-MS/MS. ESMW suppressed protein kinase A (PKA)-hormone-sensitive lipase (HSL) related lipolysis and increased AMP-activated protein kinase (AMPK) phosphorylation in PA challenged 3T3-L1 adipocytes. AMPKα knockdown abolished the inhibitory effects of ESMW on IL-6 and HSL pSer-660, revealing that the antilipolytic and anti-inflammatory activities of ESMW are AMPK dependent. Furthermore, ESMW ameliorated insulin resistance and suppressed lipolysis in HFD-fed mice. It inhibited diacylglycerol accumulation in the liver and inhibited hepatic gluconeogenesis. Conditional medium collected from ESMW-treated 3T3-L1 cells ameliorated insulin action on hepatic gluconeogenesis in liver cells, demonstrating the antilipolytic activity contributed to ESMW beneficial effects on hepatic glucose production. In conclusion, ESMW, as the antilipolytic fraction of SMW, inhibited PKA-HSL related lipolysis by activating AMPK, thus inhibiting diacylglycerol (DAG) accumulation in the liver and thereby improving insulin resistance and hepatic gluconeogenesis.


Assuntos
Insulina , Lipólise , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Insulina/metabolismo , Lipólise/fisiologia , Fígado/metabolismo , Camundongos , Espectrometria de Massas em Tandem
8.
Int J Gen Med ; 15: 3903-3914, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35431573

RESUMO

Background: To describe the characteristics of plasma lipid proliferation in cervical cancer and further evaluate the prognostic significance of lipid levels in cervical cancer. Methods: We retrospectively reviewed 1713 patients with cervical cancer in our hospital. The preoperative plasma lipid profile, including cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL), and low-density lipoprotein cholesterol (LDL), of 1713 cervical cancer patients was compared with that of 10,397 healthy women. Then, we evaluated the impact of lipids on overall survival (OS) and recurrence-free survival (RFS) in cervical cancer using univariate and multivariate Cox models. Results: While plasma TC, TG, and LDL were significantly higher, HDL was lower in patients with cervical cancer than in healthy women. TG was identified as an independent predictor for RFS and OS among patients with cervical cancer. Further stratified by age, patients with higher TGs showed a significantly worse RFS and OS than those with lower TGs among patients ≥50 years old but not among those <50 years old. Conclusion: Cervical cancer was associated with a disordered lipid profile. Hypertriglyceridemia was an independent poor prognostic indicator for cervical cancer, especially for elderly patients. Strengthening lipid management may be beneficial for improving postoperative OS and RFS in patients with cervical cancer.

9.
World J Clin Cases ; 10(8): 2497-2503, 2022 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-35434068

RESUMO

BACKGROUND: Immune checkpoint inhibitors (ICIs) targeting the programmed death (PD)-1 pathway have substantially changed the clinical management of metastatic urothelial carcinoma (mUC); however, the response rate remains low. There are ongoing efforts to identify robust biomarkers that can effectively predict the treatment response to ICIs. Previous studies have suggested that ERBB2/3 mutations are associated with the efficacy of ICIs in gallbladder carcinoma. CASE SUMMARY: We present a 59-year-old man with mUC harboring ERBB2/3 mutations (in-frame insertion of ERBB2 and ERBB3 amplification), negative PD-ligand 1 expression, and low tumor mutation burden. He received anti-PD-1 antibodies and paclitaxel as second-line treatment. After two cycles of treatment, the lung metastases had significantly shrunk, achieving good partial remission. After six cycles of combination therapy, the patient received sindilimab 200 mg once every 3 wk as maintenance monotherapy. At the last follow-up, the patient continued to exhibit a partial response and progression-free survival for as long as 19 mo. CONCLUSION: ERBB2/3 mutations may represent a predictive biomarker for selecting a subgroup of mUC patients who will benefit from ICIs.

10.
Child Dev ; 2022 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-35481708

RESUMO

This study conducts an exploratory analysis of the impacts of a center-based early childhood development intervention on the mental health of caregivers, using data from a cluster-randomized controlled trial of 1664 caregivers (Mage  = 36.87 years old) of 6- to 24-month-old children in 100 villages in rural China. Caregivers and children in 50 villages received individual parenting training, group activities and open play space in village parenting centers. The results show no significant overall change in caregiver-reported mental health symptoms after 1 year of intervention. Subgroup analyses reveal heterogeneous effects by caregiver socioeconomic status and identity (mother vs. grandmother). Findings suggest that early childhood development interventions without targeted mental health components may not provide sufficient support to improve caregiver mental health.

12.
Animals (Basel) ; 12(7)2022 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-35405822

RESUMO

Dimethoate (DT) is an environmental pollutant widely used in agricultural fields and home gardens. Studies have shown that exposure to DT causes reproductive defects in both male and female animals. However, the effects of DT exposure on oocyte maturation and the approach to counteract it are not yet known. Here, we investigated the toxicity of DT on porcine oocyte maturation and the protective effects of melatonin (MT) on DT-exposed oocytes. DT exposure with 1.5 mM partially inhibited cumulus cell expansion and significantly reduced the rate of first polar body extrusion (pb1) during oocyte maturation. Parthenogenetically activated embryos derived from DT-exposed oocytes could not develop to the 2-cell and blastocyst stage. Furthermore, DT exposure led to a significant increase in the rates of misaligned chromosomes, disorganized spindles, and abnormal actin assembly. DT exposure severely disrupted the distribution patterns of mitochondria in oocytes but did not change the subcellular localizations of cortical granules. Importantly, MT supplementation rescued the meiotic and developmental defects of DT-exposed oocytes through repressing the generation of excessive reactive oxygen species (ROS) and autophagy, and DNA damage accumulation. These results demonstrate that melatonin protects against meiotic defects induced by DT during porcine oocyte maturation.

13.
Dose Response ; 20(2): 15593258221090340, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35431698

RESUMO

Gout is a chronic disease. Gout symptoms are often experienced in the middle of the night. The onset of gout in the middle of the night is closely related to abnormal liver and gallbladder meridian. The purpose of this study was to investigate the clinical efficacy and possible mechanism of action of Tongbixiao pills in the treatment of hyperuricemia and gouty arthritis. The Tongbixiao pills we used included several traditional Chinese medicines, most of which tonify the spleen; strengthen the liver; benefit the kidney; and reduce heat, dampness, and blood stasis. In this randomized clinical study of 105 patients, we found that Tongbixiao pills can reduce uric acid levels in hyperuricemia patients. Additionally, the efficacy was similar to that of allopurinol and the level of uric acid did not increase significantly at eight weeks after withdrawal. In the absence of notable adverse reactions, Tongbixiao pills can also increase uric acid excretion, reduce serum creatinine and lipid levels, and reduce inflammation and relieve gout symptoms. In addition, we used SD rats to simulate gout and arthritis and divided them into five groups: normal group, model group, low-dose group, medium-dose group, and high-dose group. The inflammatory indices of the 40 SD rats were observed. After seven days, ankle swelling in rats in the treatment group was significantly reduced. The indices of uric acid, creatinine, and urea nitrogen in the treatment group were significantly lower than those in the model group, which proved that Tongbixiao pills could inhibit hyperuricemia in rats, thus treating gout. This study demonstrates that Tongbixiao pills can treat gout, provide more treatment options for gouty arthritis, and improve the quality of life of patients.

14.
Autism Res ; 2022 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-35403356

RESUMO

Autism spectrum disorder (ASD) is associated with altered gut microbiota. However, there has been little consensus on the altered bacterial species and studies have had small sample sizes. We aimed to identify the taxonomic composition and evaluate the changes in the fecal microbiota in Chinese children with ASD by using a relatively large sample size. We conducted a case-control study of 101 children with ASD and 103 healthy controls in China. Demographic information and fecal samples were collected, and the V3-V4 hypervariable regions of the bacterial 16S ribosomal RNA (rRNA) gene were sequenced. The alpha and beta diversities between the two groups were significantly different. After correcting for multiple comparisons, at the phylum level the relative abundances of Actinobacteria and Proteobacteria in the case group were significantly higher than those in the control group. The relative abundance of the Escherichia-Shigella genus in the case group was significantly higher than that of the control group, and the relative abundance of Blautia and unclassified_f__Lachnospiraceae in the control group were higher than that of the case group. Phylogenetic Investigation of Communities by Reconstruction of Unobserved States analysis showed that children with ASD may have disturbed functional pathways, such as amino acid metabolism, cofactor and vitamin metabolism, and the AMP-activated protein kinase signaling pathway. This study revealed the characteristics of the intestinal flora of Chinese children with ASD and provided further evidence of gut microbial dysbiosis in ASD. LAY SUMMARY: This study characterized the gut microbiota composition of 101 children with ASD and 103 healthy controls in China. The altered gut microbiota may contribute significantly to the risk of ASD, including significant increases in the relative abundances of Actinobacteria, Proteobacteria and Escherichia-Shigella and significant decrease of Blautia and unclassified_f__Lachnospiraceae. This study provided further evidence of gut microbial dysbiosis in ASD.

15.
Immunobiology ; 227(3): 152215, 2022 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-35468553

RESUMO

BACKGROUND: Corticosteroid resistance (CR) is a serious disadvantage in treating many chronic inflammatory conditions. Eosinophils are the main inflammation cells in allergic reactions. Environmental pollution, such as PM2.5, is associated with the pathogenesis of allergic disorders. The objective of this study is to elucidate the mechanism by which the exposure to PM2.5 confers eosinophil CR status. METHODS: Patients with allergic rhinitis were recruited and assigned to corticosteroid sensitive (CS) and CR groups. Eosinophils were purified from nasal lavage fluids collected from patients with allergic rhinitis. A murine AR mouse model was developed with dust mite allergens and PM2.5 as the sensitization reagents. RESULTS: CR status was detected in about 60% eosinophil collected in patients with AR. Upon exposure to eosinophil activators, CS eosinophils released a large quantity of mediators, which was suppressed by the presence of steroids in the culture. CR eosinophils demonstrated resistance to steroidal therapy. RAS activation levels in eosinophils were higher in CR eosinophils than in CS eosinophils. Higher expression of the Son of sevenless-1 (Sos1) was detected in CR eosinophils, which formed a complex with RAS and glucocorticoidreceptor-α in CR eosinophils to prevent the binding between steroids and glucocorticoidreceptor-α. The presence of an Sos1 inhibitor dissociated glucocorticoid receptor-α from RAS/Sos1 complex, that restored the sensitivity to steroids in eosinophils. Administering the Sos1 inhibitor effectively attenuated the experimental allergic rhinitis. CONCLUSIONS: CR status was detected in approximately 1/3 eosinophils sampled from patients with allergic rhinitis. Sos1 was instrumental in the development and perseverance of CR in eosinophils. Sos1 inhibition restored sensitivity to steroids in CR eosinophils, which effectively reduced experimental allergic rhinitis.

16.
Environ Sci Technol ; 56(7): 4377-4385, 2022 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-35319191

RESUMO

The efficacy of oxidation of recalcitrant organic contaminants in municipal and industrial wastewaters by ozonation is influenced by chemical reaction kinetics and hydrodynamics within a reactor. A 3D computational fluid dynamics (CFD) model incorporating both multiphase flow and reaction kinetics describing ozone decay, hydroxyl radical (•OH) generation, and organic oxidation was developed to simulate the performance of continuous flow ozonation reactors. Formate was selected as the target organic in this study due to its well-understood oxidation pathway. Simulation results revealed that the dissolved ozone concentration in the reactor is controlled by rates of O3(g) interphase transfer and ozone self-decay. Simulations of the effect of various operating conditions showed that the reaction stoichiometric constraints between formate and ozone were reached; however, complete utilization of gas phase ozone was hard to achieve due to the low ozone interphase mass transfer rate. Increasing the O3(g) concentration leads to an increase in the formate removal rate by ∼5% due to an enhancement in the rate of O3(g) interphase mass transfer. The CFD model adequately describes the mass transfer occurring in the two-phase flow system and confirms that O3(g) interphase mass transfer is the rate-limiting step in contaminant degradation. The model can be used to optimize the ozone reactor design for improved contaminant degradation and ozonation efficiency.


Assuntos
Ozônio , Poluentes Químicos da Água , Purificação da Água , Hidrodinâmica , Cinética , Oxirredução , Ozônio/análise , Poluentes Químicos da Água/análise , Purificação da Água/métodos
17.
Gene ; 827: 146460, 2022 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-35358657

RESUMO

Sinapine (SI) is a naturally occurring product with biological properties, but its activity against non-small cell lung cancer (NSCLC) remains unclear. This research examined the anti-tumour effects of SI in NSCLC cells and the underlying mechanisms of any effects. SI induced ferroptosis, a novel form of cell death, by increasing intracellular ferrous iron, lipid peroxidation, and reactive oxygen species (ROS) in NSCLC cells. SI treatment resulted in transferrin and transferrin receptor upregulation, and inhibition of transferrin or the transferrin receptor reduced the ferroptosis caused by SI. SI treatment also resulted in a p-53 dependent downregulation of SLC7A11. Finally, we evaluated the effects of SI in vivo and it was found that SI also successfully inhibited the growth of NSCLC in vivo. In summary, our data demonstrated that SI triggered ferroptosis in NSCLC cells and may be a promising therapeutic agent for this condition.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Ferroptose , Neoplasias Pulmonares , Sistema y+ de Transporte de Aminoácidos/genética , Sistema y+ de Transporte de Aminoácidos/metabolismo , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Colina/análogos & derivados , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Receptores da Transferrina/genética , Receptores da Transferrina/uso terapêutico , Transferrina
18.
J Antimicrob Chemother ; 77(5): 1286-1295, 2022 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-35296898

RESUMO

OBJECTIVES: To investigate the prevalence and molecular characteristics of fosA3 and fosA7 among Salmonella isolates. METHODS: Five hundred and fifty-one Salmonella isolates collected from food animals in China during 2016-19 were screened for fos genes. The drug resistance, serovars, clonal relationships and genetic environments of fosA were compared between fosA7- and fosA3-positive Salmonella. RESULTS: A relatively high prevalence of fosA7 (9.26%) and fosA3 (6.53%) was identified. fosA3 was associated with high-level fosfomycin resistance (≥512 mg/L), while fosA7 conferred relatively low-level resistance that was independent of the presence of glucose-6-phosphate. Additionally, fosA7 could facilitate Salmonella survival under oxidative stress. Both fosA3 and fosA7 were found in diverse serovars and STs, but segregated into distinct groups. The fosA3-positive Salmonella Typhimurium/Salmonella Indiana strains showed close genetic relationships, while fosA7-positive Salmonella Meleagridis/Salmonella Agona/Salmonella Derby showed a relatively high degree of whole-genome sequence heterogeneity. fosA3 was located on conjugative IncHI2 plasmids or chromosomes, while fosA7 was strictly chromosomal. Furthermore, two strains carried large chromosomal fosA7 regions within genomic islands. The fosA3 and fosA7 contigs from our isolates and the NCBI could be segregated into four primary and distinct genomic backbones. IS26 and the antibiotic resistance genes (ARGs) blaCTX-M, blaTEM-1B and rmtB were frequently adjacent to fosA3, while fosA7-carrying contigs generally lacked mobile elements and ARGs. CONCLUSIONS: fosA3 and fosA7 were the primary factors contributing to reduced fosfomycin susceptibility, to different degrees, in these Salmonella isolates. The distinct distributions and molecular characteristics of fosA7 and fosA3 indicated that their origin and evolution in Salmonella were most likely distinct.


Assuntos
Fosfomicina , Animais , Antibacterianos/farmacologia , China/epidemiologia , Escherichia coli/genética , Testes de Sensibilidade Microbiana , Plasmídeos , Prevalência , Salmonella/genética , beta-Lactamases/genética
19.
Front Immunol ; 13: 801909, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35309350

RESUMO

Background: Anti-programmed cell death protein 1 and its ligand (anti-PD1/PDL1) have been proposed as a promising therapeutic option for advanced biliary tract cancer (aBTC). Given the scarce quantitative analyses of anti-PD1/PDL1 in aBTC, we thus did a meta-analysis to assess the benefits and risks of this emerging treatment strategy in patients with aBTC. Methods: PubMed, Embase, the Cochrane Library, Web of Science, and meeting resources were searched for relevant studies. The main endpoints were median progression-free survival (mPFS), median overall survival (mOS), objective response rate (ORR), disease control rate (DCR), any-grade adverse events (AEs), and grade 3-4 AEs. Results: Twenty-eight studies with 1,338 participants were included. The best curative effect was found in the anti-PD1/PDL1 combined with anti-CTLA4 and chemotherapy group (mPFS: 12.4 months; mOS: 16.0 months; ORR: 45.1%; DCR: 95.0%), followed by the anti-PD1/PDL1 plus chemotherapy group (mPFS: 8.2 months; mOS: 14.8 months; ORR: 36.3%; DCR: 84.6%), the anti-PD1/PDL1 plus antiangiogenesis group (mPFS: 4.9 months; mOS: 10.2 months; ORR: 17.5%; DCR: 68.7%), the anti-PD1/PDL1 plus anti-cytotoxic T lymphocyte antigen 4 (anti-CTLA4) group (mPFS: 2.9 months; mOS: 8.3 months; ORR: 9.9%; DCR: 36.8%), and the anti-PD1/PDL1 monotherapy group (mPFS: 2.5 months; mOS: 7.6 months; ORR: 6.8%; DCR: 34.7%). Compared with anti-PD1-containing regimens, anti-PDL1-containing regimens achieved preferable mPFS (11.1 vs. 3.8 months), mOS (12.2 vs. 9.8 months), and ORR (23.7% vs. 17.4%), despite a similar DCR (61.1% vs. 61.3%). The mPFS, mOS, ORR, and DCR were 10.6 months, 15.8 months, 42.3%, and 88.6% of first-line anti-PD1/PDL1 and 3.0 months, 9.1 months, 11.6%, and 51.1% of second-line therapy or beyond, respectively. There were 80.6% and 34.0% of the patients suffering any-grade AEs and grade 3-4 AEs. Anti-PD1/PDL1 monotherapy might be considered as a safer alternative than combination regimens. Meanwhile, obvious toxicities in the first-line setting could not be neglected. Conclusions: Anti-PD1/PDL1 showed encouraging efficacy and acceptable safety profile in aBTC and, thus, could be an alternative treatment.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias do Sistema Biliar , Anticorpos Monoclonais Humanizados/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Sistema Biliar/tratamento farmacológico , Humanos , Intervalo Livre de Progressão
20.
Front Pharmacol ; 13: 817235, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35281920

RESUMO

[This corrects the article DOI: 10.3389/fphar.2021.740057.].

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