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2.
Chin J Integr Med ; 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38910189

RESUMO

OBJECTIVE: To examine the effectiveness of Chinese medicine (CM) Lianhua Qingwen Granule (LHQW) and Jingyin Gubiao Prescription (JYGB) in asymptomatic or mild patients with Omicron infection in the shelter hospital. METHODS: This single-center retrospective cohort study was conducted in the largest shelter hospital in Shanghai, China, from April 10, 2022 to May 30, 2022. A total of 56,244 asymptomatic and mild Omicron cases were included and divided into 4 groups, i.e., non-administration group (23,702 cases), LHQW group (11,576 cases), JYGB group (12,112 cases), and dual combination of LHQW and JYGB group (8,854 cases). The length of stay (LOS) in the hospital was used to assess the effectiveness of LHQW and JYGB treatment on Omicron infection. RESULTS: Patients aged 41-60 years, with nadir threshold cycle (CT) value of N gene <25, or those fully vaccinated preferred to receive CM therapy. Before or after propensity score matching (PSM), the multiple linear regression showed that LHQW and JYGB treatment were independent influence factors of LOS (both P<0.001). After PSM, there were significant differences in LOS between the LHQW/JYGB combination and the other groups (P<0.01). The results of factorial design ANOVA proved that the LHQW/JYGB combination therapy synergistically shortened LOS (P=0.032). CONCLUSIONS: Patients with a nadir CT value <25 were more likely to accept CM. The LHQW/JYGB combination therapy could shorten the LOS of Omicron-infected individuals in an isolated environment.

3.
BMC Genom Data ; 25(1): 60, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38877416

RESUMO

BACKGROUND: Forest geneticists typically use provenances to account for population differences in their improvement schemes; however, the historical records of the imported materials might not be very precise or well-aligned with the genetic clusters derived from advanced molecular techniques. The main objective of this study was to assess the impact of marker-based population structure on genetic parameter estimates related to growth and wood properties and their trade-offs in Norway spruce, by either incorporating it as a fixed effect (model-A) or excluding it entirely from the analysis (model-B). RESULTS: Our results indicate that models incorporating population structure significantly reduce estimates of additive genetic variance, resulting in substantial reduction of narrow-sense heritability. However, these models considerably improve prediction accuracies. This was particularly significant for growth and solid-wood properties, which showed to have the highest population genetic differentiation (QST) among the studied traits. Additionally, although the pattern of correlations remained similar across the models, their magnitude was slightly lower for models that included population structure as a fixed effect. This suggests that selection, consistently performed within populations, might be less affected by unfavourable genetic correlations compared to mass selection conducted without pedigree restrictions. CONCLUSION: We conclude that the results of models properly accounting for population structure are more accurate and less biased compared to those neglecting this effect. This might have practical implications for breeders and forest managers where, decisions based on imprecise selections can pose a high risk to economic efficiency.


Assuntos
Picea , Madeira , Picea/genética , Picea/crescimento & desenvolvimento , Madeira/genética , Marcadores Genéticos/genética , Modelos Genéticos , Genética Populacional/métodos , Variação Genética/genética
4.
3D Print Addit Manuf ; 11(2): e655-e665, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38689901

RESUMO

This article investigates a laser-directed energy deposition additive manufacturing (AM) method, based on coaxial powder feeding, for preparing quartz glass. Through synergistic optimization of line deposition and plane deposition experiments, key parameters of laser coaxial powder feeding AM were identified. The corresponding mechanical properties, thermal properties, and microstructure of the bulk parts were analyzed. The maximum mechanical strength of the obtained quartz glass element reached 72.36 ± 5.98 MPa, which is ca. 95% that of quartz glass prepared by traditional methods. The thermal properties of the obtained quartz glass element were also close to those prepared by traditional methods. The present research indicates that one can use laser AM technology that is based on coaxial powder feeding to form quartz glass with high density and good thermodynamic properties. Such quartz glass has substantial potential in, for example, optics and biomedicine.

5.
Int Wound J ; 21(4): e14834, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38650426

RESUMO

A meta-analysis was conducted comprehensively to investigate the impact of evidence-based nursing (EBN) interventions on pressure injury (PI) in the intensive care unit (ICU) patients. Computer searches were performed, from databases inception to November 2023, in Wanfang, PubMed, China National Knowledge Infrastructure, Google Scholar, Embase, and Cochrane Library for randomized controlled trials (RCTs) on the application of EBN interventions in ICU patients. Two independent researchers conducted screenings of the literature, extracted data, and carried out quality evaluations. Stata 17.0 software was employed for data analysis. Overall, 25 RCTs, involving 2494 ICU patients, were included. It was found that compared to conventional care methods, the implementation of EBN interventions in ICU patients markedly decreased the occurrence of PI (odds ratio [OR]: 0.22, 95% confidence interval [CI]: 0.17-0.30, p < 0.001), delayed the onset time of pressure ulcers (standardized mean difference [SMD]: -1.61, 95% CI: -2.00 to -1.22, p < 0.001), and also improved nursing satisfaction (OR: 1.18, 95% CI: 1.14-1.23, p < 0.001). Our findings suggest the implementation of EBN interventions in the care of PI in ICU patients is highly valuable, can reduce the occurrence of PI, can delay the time of appearance, and is associated with relatively higher nursing satisfaction, making it worthy of promotion.


Assuntos
Enfermagem Baseada em Evidências , Unidades de Terapia Intensiva , Úlcera por Pressão , Úlcera por Pressão/enfermagem , Úlcera por Pressão/prevenção & controle , Humanos , Enfermagem Baseada em Evidências/métodos , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Idoso , Ensaios Clínicos Controlados Aleatórios como Assunto
6.
Mol Biol Evol ; 41(2)2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38243850

RESUMO

Local adaptation is critical in speciation and evolution, yet comprehensive studies on proximate and ultimate causes of local adaptation are generally scarce. Here, we integrated field ecological experiments, genome sequencing, and genetic verification to demonstrate both driving forces and molecular mechanisms governing local adaptation of body coloration in a lizard from the Qinghai-Tibet Plateau. We found dark lizards from the cold meadow population had lower spectrum reflectance but higher melanin contents than light counterparts from the warm dune population. Additionally, the colorations of both dark and light lizards facilitated the camouflage and thermoregulation in their respective microhabitat simultaneously. More importantly, by genome resequencing analysis, we detected a novel mutation in Tyrp1 that underpinned this color adaptation. The allele frequencies at the site of SNP 459# in the gene of Tyrp1 are 22.22% G/C and 77.78% C/C in dark lizards and 100% G/G in light lizards. Model-predicted structure and catalytic activity showed that this mutation increased structure flexibility and catalytic activity in enzyme TYRP1, and thereby facilitated the generation of eumelanin in dark lizards. The function of the mutation in Tyrp1 was further verified by more melanin contents and darker coloration detected in the zebrafish injected with the genotype of Tyrp1 from dark lizards. Therefore, our study demonstrates that a novel mutation of a major melanin-generating gene underpins skin color variation co-selected by camouflage and thermoregulation in a lizard. The resulting strong selection may reinforce adaptive genetic divergence and enable the persistence of adjacent populations with distinct body coloration.


Assuntos
Lagartos , Melaninas , Animais , Melaninas/genética , Lagartos/genética , Peixe-Zebra , Regulação da Temperatura Corporal/genética , Pigmentação da Pele/genética , Cor
7.
J Cell Mol Med ; 28(1): e17983, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38070189

RESUMO

Gastric cancer results in great cancer mortality worldwide, and inducing ferroptosis dramatically improves the malignant phenotypes of gastric cancer. DNA polymerase epsilon subunit 2 (POLE2) plays indispensable roles in tumorigenesis; however, its involvement and molecular basis in ferroptosis and gastric cancer are not clear. Human gastric cancer cells were infected with lentiviral vectors to knock down or overexpress POLE2, and cell ferroptosis was detected. To further validate the involvement of nuclear factor erythroid 2-related factor 2 (NRF2) and glutathione peroxidase 4 (GPX4), lentiviral vectors were used. POLE2 expression was elevated in human gastric cancer cells and tissues and closely correlated with clinicopathological features in gastric cancer patients. POLE2 knockdown was induced, while POLE2 overexpression inhibited ferroptosis of human gastric cancer cells, thereby modulating the malignant phenotypes of gastric cancer. Mechanistic studies revealed that POLE2 overexpression elevated NRF2 expression and activity and subsequently activated GPX4, which then prevented lipid peroxidation and ferroptosis in human gastric cancer cells. In contrast, either NRF2 or GPX4 silence significantly prevented POLE2 overexpression-mediated inductions of cell proliferation, migration, invasion and inhibition of ferroptosis. POLE2 overexpression inhibits ferroptosis in human gastric cancer cells through activating NRF2/GPX4 pathway, and inhibiting POLE2 may be a crucial strategy to treat gastric cancer.


Assuntos
Ferroptose , Neoplasias Gástricas , Humanos , Lentivirus , Fator 2 Relacionado a NF-E2 , Nucleotidiltransferases , Subunidades Proteicas
8.
Nat Commun ; 14(1): 8357, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-38102128

RESUMO

Teleost fishes, which are the largest and most diverse group of living vertebrates, have a rich history of ancient and recent polyploidy. Previous studies of allotetraploid common carp and goldfish (cyprinids) reported a dominant subgenome, which is more expressed and exhibits biased gene retention. However, the underlying mechanisms contributing to observed 'subgenome dominance' remains poorly understood. Here we report high-quality genomes of twenty-one cyprinids to investigate the origin and subsequent subgenome evolution patterns following three independent allopolyploidy events. We identify the closest extant relatives of the diploid progenitor species, investigate genetic and epigenetic differences among subgenomes, and conclude that observed subgenome dominance patterns are likely due to a combination of maternal dominance and transposable element densities in each polyploid. These findings provide an important foundation to understanding subgenome dominance patterns observed in teleost fishes, and ultimately the role of polyploidy in contributing to evolutionary innovations.


Assuntos
Carpas , Evolução Molecular , Animais , Poliploidia , Genoma/genética , Epigênese Genética , Genoma de Planta
9.
Rev Sci Instrum ; 94(11)2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37934035

RESUMO

Coaxial peaking capacitor is a key component in high-altitude electromagnetic pulse (EMP) simulators with fast front pulse output. It poses significant technical and engineering challenges in limiting radiation field amplitude and test space. This paper presents the design and testing of a 180 pF, 3 MV coaxial peaking capacitor with improved insulation performance. In the insulation design, the length of the dielectric film is extended to reduce the background electric field on the flashover path. The electric field threshold obtained from image diagnosis is used as a reference. During capacitor testing, the insulation characteristics are diagnosed using both direct and indirect methods. The voltage measured by a D-dot probe, the output waveform of the Marx generator in the primary source, and the radiation field waveform are analyzed to understand the flashover characteristics of the capacitor and to improve the reliability of the test results. The experimental results demonstrate that the peaking capacitor can operate stably at 3.0 MV. If flashover occurring on the dropping edge of the pulse is permitted, the operating voltage can be greater than 3.7 MV without significantly affecting the radiation field waveform. The analysis on the surface flashover morphology of the peaking capacitor reveals that the flashover mainly occurs at the dropping edge of the capacitor's waveform, indicating that the damage to the film is not serious. This research significantly increases the working voltage of coaxial peaking capacitors and contributes to the development of high-altitude EMP simulation technology.

10.
Asian J Androl ; 25(6): 745-749, 2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-37282382

RESUMO

To compare the impact of the scrotal vs inguinal orchidopexy approach on the testicular function of infants with cryptorchidism, a randomized controlled trial was conducted involving boys who were 6-12 months old at surgery and were diagnosed with clinically palpable, inguinal undescended testis. Between June 2021 and December 2021, these boys at Fujian Maternity and Child Health Hospital (Fuzhou, China) and Fujian Children's Hospital (Fuzhou, China) were enrolled. Block randomization with a 1:1 allocation ratio was employed. The primary outcome was testicular function assessed by testicular volume, serum testosterone, anti-Müllerian hormone (AMH), and inhibin B (InhB) levels. Secondary outcomes included operative time, amount of intraoperative bleeding, and postoperative complications. Among 577 screened patients, 100 (17.3%) were considered eligible and enrolled in the study. Of the 100 children who completed the 1-year follow-up, 50 underwent scrotal orchidopexy and 50 underwent inguinal orchidopexy. The testicular volume, serum testosterone, AMH, and InhB levels in both groups increased markedly after surgery (all P < 0.05), but there were no apparent differences between groups at 6 months and 12 months after operation (all P > 0.05). No differences between the scrotal and inguinal groups were noted regarding the operative time ( P = 0.987) and amount of intraoperative bleeding ( P = 0.746). The overall complication rate (2.0%) of the scrotal group was slightly lower than that of the inguinal group (8.0%), although this difference was not statistically significant ( P > 0.05). Both scrotal and inguinal orchiopexy exerted protective effects on testicular function in children with cryptorchidism, with similar operative status and postoperative complications. Scrotal orchiopexy is an effective alternative to inguinal orchiopexy in children with cryptorchidism.


Assuntos
Criptorquidismo , Feminino , Gravidez , Masculino , Lactente , Humanos , Criança , Criptorquidismo/cirurgia , Orquidopexia , Escroto/cirurgia , Complicações Pós-Operatórias , Hormônio Antimülleriano , Testosterona
11.
Int J Biol Macromol ; 244: 125409, 2023 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-37327936

RESUMO

Dynamin-related protein 1 (DRP1) is a key regulator in the maintenance of mammalian glucose homeostasis, but the relevant information remains poorly understood on aquatic animals. In the study, DRP1 is formally described for the first time in Oreochromis niloticus. DRP1 encodes a peptide of 673 amino acid residues that contained three conserved domains: a GTPase domain, a dynamin middle domain and a dynamin GTPase effector domain. DRP1 transcripts are widely distributed in all of the detected seven organs/tissues, and the highest mRNA levels in brain. High-carbohydrate (45 %) fed fish showed a significant upregulation of liver DRP1 expression than that of control (30 %) group. Glucose administration upregulated liver DRP1 expression, with peak values observed at 1 h; then its expression returned to the basal value at 12 h. In the in vitro study, DRP1 over-expression significantly decreased mitochondrial abundance in hepatocytes. DHA significantly increased mitochondrial abundance, transcriptions of mitochondrial transcription factor A (TFAM) and mitofusin 1 and 2 (MFN1 and MFN2) and complex II and III activities of high glucose-treated hepatocyte, whereas the opposite was true for DRP1, mitochondrial fission factor (MFF) and fission (FIS) expression. Together, these findings illustrated that O. niloticus DRP1 is highly conserved, and it participated in glucose control of fish. DHA could alleviate high glucose-induced mitochondrial dysfunction of fish by inhibiting DRP1-mediated mitochondrial fission.


Assuntos
Ciclídeos , Dinâmica Mitocondrial , Animais , Ciclídeos/genética , Ciclídeos/metabolismo , Dinaminas/genética , Dinaminas/química , Dinaminas/metabolismo , GTP Fosfo-Hidrolases/genética , GTP Fosfo-Hidrolases/química , GTP Fosfo-Hidrolases/metabolismo , Mitocôndrias/metabolismo , Proteínas Mitocondriais/genética , Mamíferos/metabolismo
12.
Expert Rev Gastroenterol Hepatol ; 17(6): 623-633, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37148261

RESUMO

BACKGROUND: Tenofovir (TDF) and entecavir (ETV) are first-line treatments for patients with chronic hepatitis B virus (HBV) infection. However, the effect of TDF versus ETV on the prognosis of HBV-related hepatocellular carcinoma (HCC) has not been fully clarified yet. RESEARCH DESIGN AND METHODS: PubMed, Embase and Web of science were searched up to March, 2021. Meta-analyses were performed for overall survival (OS), disease-free survival (DFS) and recurrence-free survival (RFS) to assess the effect of TDF versus ETV on the prognosis of HBV-related HCC. RESULTS: A total of 10 studies comprising 4706 Asian patients were included. The pooled results revealed that TDF was associated with better OS (adjusted HR = 0.50, 95% CI: 0.40-0.62; I2 = 36.0%, p = 0.167) and better RFS/DFS (adjusted HR = 0.70, 95% CI: 0.55-0.89, I2 = 71.9%, p = 0.002) than ETV in treatment of HBV-related HCC. Subgroup analysis revealed that OS benefit from TDF was generally consistent, except for patients who underwent non-surgical treatment for HCC. Subgroup analysis also indicated that TDF reduces the risk of late recurrence (HR = 0.41, 95% CI: 0.18-0.0.93; I2 = 63.0%, p = 0.067) rather than early recurrence (HR = 0.99, 95% CI: 0.64-1.52; I2 = 61.3%, p = 0.076). CONCLUSIONS: Compared with ETV, TDF has the advantage of improving OS and reducing late recurrence of patients with HBV-related HCC patients who underwent resection.


Assuntos
Carcinoma Hepatocelular , Hepatite B Crônica , Neoplasias Hepáticas , Humanos , Tenofovir/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Vírus da Hepatite B/genética , Hepatite B Crônica/complicações , Hepatite B Crônica/diagnóstico , Hepatite B Crônica/tratamento farmacológico , Antivirais/efeitos adversos , Neoplasias Hepáticas/tratamento farmacológico , Prognóstico , Resultado do Tratamento
13.
Immunotherapy ; 15(9): 669-678, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37140011

RESUMO

Aims: This work was designed to identify the subgroup of advanced hepatocellular carcinoma (HCC) patients for whom treatments containing immune checkpoint blockers (ICBs) were most effective. Materials & methods: A meta-analysis was performed to explore the subgroup population with the greatest benefit of treatments containing ICBs. Results: A total of 2228 patients from four randomized control trials were included. Treatments containing ICBs had better overall survival, progression-free survival and higher objective response rate over treatment without ICBs. Subgroup analysis revealed that treatments containing ICBs were highly effective in improving the overall survival of males, patients with macrovascular invasion and/or extrahepatic spread and viral-related HCC patients. Conclusion: Treatments containing ICBs are more effective for males, patients with macrovascular invasion and/or extrahepatic spread and viral-related HCC patients.


Immune checkpoint blockers (ICBs) have significantly improved the prognosis of advanced cancers. However, some patients still cannot benefit from ICBs. The use of ICBs in the treatment of advanced hepatocellular carcinoma (HCC) started late. The subgroup of advanced HCC patients that will benefit most from treatments containing ICBs is still largely unknown. Therefore, a meta-analysis (meta-analysis is a statistical method used to compare or synthesize research results on the same scientific problem) was performed to explore the subgroup population with the greatest benefit of treatments containing ICBs (ICBs alone or in combination with anti-VEGF agents). The results show that treatments containing ICBs are more effective for males, patients with macrovascular invasion and/or extrahepatic spread and viral-related HCC patients.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Masculino , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/terapia , Inibidores de Checkpoint Imunológico/uso terapêutico , Intervalo Livre de Progressão
14.
Heliyon ; 9(3): e14307, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36950649

RESUMO

Introduction: Hepatocellular carcinoma (HCC) is one of the most common malignant tumours worldwide. Clarification of the somatic mutational landscape of important genes could reveal new therapeutic targets and facilitate individualized therapeutic approaches for HCC patients. The mutation and expression changes in the ARID1A gene in HCC remain controversial. Methods: First, cBioPortal was used to visualize genetic alterations and DNA copy number alterations (CNAs) in ARID1A. The relationships between ARID1A mutation status and HCC patient clinicopathological features and overall survival (OS) were also determined. Then, a meta-analysis was performed to evaluate the effect of ARID1A mutation or expression on the prognosis of HCC patients. Finally, the role of ARID1A in HCC progression was verified by in vitro experiments. Results: ARID1A mutation was detected in 9.35% (33/353) of sequenced HCC cases, and ARID1A mutation decreased ARID1A mRNA expression. Patients with ARID1A alterations presented worse OS than those without ARID1A alterations. Meta-analysis and human HCC tissue microarray (TMA) analysis revealed that HCC patients with low ARID1A expression had worse OS and relapse-free survival (RFS), and low ARID1A expression was negatively correlated with tumour size. Then, ARID1A gain-of-function and loss-of-function experiments demonstrated the tumour suppressor role of ARID1A in HCC in vitro. In terms of the mechanism, we found that ARID1A could inhibit HCC progression by regulating retinoblastoma-like 1 (RBL1) expression via the JNK/FOXO3 pathway. Conclusions: ARID1A can be considered a potential prognostic biomarker and candidate therapeutic target for HCC.

15.
BMC Genomics ; 24(1): 147, 2023 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-36973641

RESUMO

Genomic prediction (GP) or genomic selection is a method to predict the accumulative effect of all quantitative trait loci (QTLs) in a population by estimating the realized genomic relationships between the individuals and by capturing the linkage disequilibrium between markers and QTLs. Thus, marker preselection is considered a promising method to capture Mendelian segregation effects. Using QTLs detected in a genome-wide association study (GWAS) may improve GP. Here, we performed GWAS and GP in a population with 904 clones from 32 full-sib families using a newly developed 50 k SNP Norway spruce array. Through GWAS we identified 41 SNPs associated with budburst stage (BB) and the largest effect association explained 5.1% of the phenotypic variation (PVE). For the other five traits such as growth and wood quality traits, only 2 - 13 associations were observed and the PVE of the strongest effects ranged from 1.2% to 2.0%. GP using approximately 100 preselected SNPs, based on the smallest p-values from GWAS showed the greatest predictive ability (PA) for the trait BB. For the other traits, a preselection of 2000-4000 SNPs, was found to offer the best model fit according to the Akaike information criterion being minimized. But PA-magnitudes from GP using such selections were still similar to that of GP using all markers. Analyses on both real-life and simulated data also showed that the inclusion of a large QTL SNP in the model as a fixed effect could improve PA and accuracy of GP provided that the PVE of the QTL was ≥ 2.5%.


Assuntos
Picea , Locos de Características Quantitativas , Humanos , Estudo de Associação Genômica Ampla/métodos , Desequilíbrio de Ligação , Genômica/métodos , Fenótipo , Picea/genética , Noruega , Polimorfismo de Nucleotídeo Único , Genótipo
16.
Exp Hematol Oncol ; 12(1): 17, 2023 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-36747292

RESUMO

BACKGROUND: Hypoxia is a hallmark of cancer, and is closely intertwined with tumor immune evasion. Circular RNAs (circRNAs) have been implicated in tumor response to immune checkpoint blockades. However, hypoxia-associated circRNAs that orchestrate the association between hypoxia and response to immunotherapy remain poorly understood. Here, we aimed to determine the roles of hypoxia-associated circRNAs in immune escape of hepatocellular carcinoma (HCC) cells. METHODS: Differentially expressed hypoxia-associated circRNAs were determined using high-throughput sequencing technology. HCC patients treated with PD-1 blockade were enrolled to assess the clinical significance of circPRDM4. RT-qPCR, western blotting, flow cytometry, T cell-mediated tumor cell killing assay, and enzyme linked immunosorbent assay were used to investigate the roles of circPRDM4 in immune escape of HCC cells in vitro. Patient-derived xenograft mouse models and adoptive human tumor infiltrating lymphocyte-CD8+ T cell transfer were adopted to evaluate the effects of circPRDM4 in vivo. RNA pull-down, mass spectrometry, RNA immunoprecipitation, chromatin immunoprecipitation, chromatin isolation by RNA purification, dual-luciferase reporter assays, dot blotting, DNA in situ hybridization, and immunoprecipitation were utilized to examine the interaction between circPRDM4, HIF-1α, and CD274 promoter. RESULTS: We identified circPRDM4 as a hypoxia-associated circRNA in HCC. circPRDM4 was upregulated in responders to PD-1 blockade and associated with therapeutic efficacy. In vitro and in vivo experiments showed that circPRDM4 induced PD-L1 expression and promoted CD8+ T cell-mediated immune escape under hypoxic conditions. Mechanistically, circPRDM4 acted as a scaffold to recruit HIF-1α onto CD274 promoter, and cemented their interaction, ultimately promoting the HIF-1α-mediated transactivation of PD-L1. CONCLUSIONS: These findings illustrated that circPRDM4 promoted immune escape of HCC cells by facilitating the recruitment of HIF-1α onto the promoter of CD274 under hypoxia, thereby inhibiting CD8+ T cell infiltration in the tumor microenvironment. This work may provide a novel prognostic biomarker and therapeutic candidate for HCC immunotherapy.

17.
Cancer Immunol Immunother ; 72(7): 1957-1969, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36811662

RESUMO

BACKGROUND AND AIMS: The impacts of macrovascular invasion (MVI) or extrahepatic spread (EHS) on the efficacy and safety of immune checkpoint inhibitors (ICIs) among hepatocellular carcinoma (HCC) patients remain unclear. Thus, we conducted a systematic review and meta-analysis to clarify whether ICI therapy is a feasible treatment option for HCC with MVI or EHS. METHODS: Eligible studies published before September 14, 2022, were retrieved. In this meta-analysis, the objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and occurrence of adverse events (AEs) were outcomes of interest. RESULTS: Fifty-four studies involving 6187 individuals were included. The findings indicated that the presence of EHS in ICI-treated HCC patients may indicate an inferior ORR (OR 0.77, 95% CI 0.63-0.96), but may not significantly affect the PFS (multivariate analyses: HR 1.27, 95% CI 0.70-2.31) and OS (multivariate analyses: HR 1.23, 95% CI 0.70-2.16). Additionally, the presence of MVI in ICI-treated HCC patients may not have significant prognostic impact on ORR (OR 0.84, 95% CI 0.64-1.10), but may indicate inferior PFS (multivariate analyses: HR 1.75, 95% CI 1.07-2.84) and OS (multivariate analyses: HR 2.03, 95% CI 1.31-3.14). The presence of EHS or MVI in ICI-treated HCC patients may not significantly impact the occurrence of any serious immune-related adverse events (irAEs) (grades ≥ 3) (EHS: OR 0.44, 95% CI 0.12-1.56; MVI: OR 0.68, 95% CI 0.24-1.88). CONCLUSION: The presence of MVI or EHS in ICI-treated HCC patients may not significantly impact the occurrence of serious irAEs. However, the presence of MVI (but not EHS) in ICI-treated HCC patients may be a significant negative prognostic factor. Therefore, ICI-treated HCC patients with MVI warrant more attention.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patologia , Inibidores de Checkpoint Imunológico/efeitos adversos , Neoplasias Hepáticas/patologia , Prognóstico
18.
Technol Health Care ; 31(3): 1093-1103, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36617804

RESUMO

BACKGROUND: Coronary artery bypass graft (CABG) and percutaneous coronary intervention (PCI) are the main treatment methods for left main artery disease (LMAD) and triple-vessel coronary artery disease (TVCAD). OBJECTIVE: This study aimed to evaluate the five-year post-treatment effects of CABG and PCI in patients with severe coronary vasculopathy. METHODS: A total of 430 patients with LMAD and/or triple-vessel coronary artery disease from November 2014 to July 2015 were enrolled retrospectively in the affiliated cardiovascular hospital of Shanxi Medical University and divided into the CABG group and PCI group. The living conditions of the patients were obtained through medical records and telephonic follow-ups five years after the surgery date. The independent risk factors for major adverse cardiovascular and cerebrovascular events (MACCE) were analyzed using logistic regression analysis. The effects of the two treatment methods were followed up and evaluated to measure the predictive ability of the Global Risk Classification (GRC) scoring system for MACCE after five years. RESULTS: There were 212 cases in the CABG group and 218 cases in the PCI group. Smoking (P= 0.047), diabetes (P= 0.031), LVEF (P= 0.020), LMAD (P= 0.008), and anterior descending branch lesions (P= 0.038) were significantly correlated with MACCE. The prevalence of MACCE in the CABG group and PCI group had no significant difference (P= 0.549). The GRC scoring system received an AUC of 0.701 for predicting MACCE. CONCLUSION: For patients with severe coronary artery disease, there was no significant difference in the prevalence of MACCE between the CABG and the PCI groups. Several independent risk factors for MACCE were found. The GRC scoring system showed a strong predictive ability for MACCE after five years of revascularization.


Assuntos
Doença da Artéria Coronariana , Intervenção Coronária Percutânea , Humanos , Artérias , Doença da Artéria Coronariana/cirurgia , Seguimentos , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/métodos , Estudos Retrospectivos , Resultado do Tratamento
19.
Expert Rev Gastroenterol Hepatol ; 17(2): 189-198, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36625022

RESUMO

BACKGROUND: Fatty liver (FL) is reportedly a risk factor for hepatocellular carcinoma (HCC) in individuals affected with Hepatitis C (HCV) or B (HBV) virus. However, the results are contradictory, necessitating a meta-analysis. RESEARCH DESIGN AND METHODS: Sixteen relevant studies involving 88,618 individuals were retrieved from the Cochrane Library, PubMed, MEDLINE, Embase, and Scopus databases from their inception to 10 December 2022. The hazard ratios (HR) and 95% confidence intervals (CI) were analyzed. RESULTS: Liver biopsy-proven FL may be a significant risk factor for HCC in individuals affected with HBV (univariate analyses: HR = 3.13, 95% CI = 1.69-5.79; multivariate analyses: HR = 3.42, 95% CI = 0.83-14.09) as well as HCV (univariate analyses: HR = 1.64, 95% CI = 0.93-2.90; multivariate analyses: HR = 1.75, 95% CI = 1.02-3.00). However, the presence of FL confirmed using reasonable methods other than liver biopsy may not indicate a risk for HCC in HBV-infected individuals (univariate analyses: HR = 0.90, 95% CI = 0.44-1.81; multivariate analyses: HR = 0.69, 95% CI = 0.45-1.08). CONCLUSIONS: Biopsy-proven FL may be a significant risk factor for HCC in HCV/HBV-infected individuals. Thus, such individuals should receive suitable interventions to prevent HCC formation or at least attenuate the risk of HCC.


Assuntos
Carcinoma Hepatocelular , Fígado Gorduroso , Hepatite C , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/etiologia , Vírus da Hepatite B , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/etiologia , Hepatite C/complicações , Hepatite C/epidemiologia , Hepacivirus , Fígado Gorduroso/epidemiologia
20.
J Cancer Res Clin Oncol ; 149(4): 1425-1441, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35482077

RESUMO

BACKGROUND: Tumor vaccines for hepatocellular carcinoma (HCC) is an area of intense interest. Tremendous clinical trials have been conducted globally, but the efficacy and security of tumor vaccines are elusive. The aim of our study was to evaluate the efficacy and security of tumor vaccines. METHODS: All relevant studies were identified in PubMed, EMBASE, Web of science and Cochrane Library databases. Objective response rate (ORR), median overall survival (OS), or median progression-free survival (PFS) and 95% CI were meta-analyzed based on the random-effects model. The individual-level data of OS, PFS were pooled by conducting survival analysis. All observed adverse events were collected. RESULTS: 31 studies containing 35 eligible cohorts with 932 HCC patients were included. The pooled ORR were 7% (95% CI 3-14%), while ORR of dendritic cell (DC) vaccine (19%, 95% CI 11-29%) were highly significant than ORR of peptide vaccine (1%, 95% CI 0-5%). The pooled median OS and PFS were 13.67 months (95% CI 8.20-22.80) and 6.19 months (95% CI 2.97-12.91), respectively. The pooled median OS (DC vaccine: median OS = 21.77 months, 95% CI 18.33-25.86; Peptide vaccine: median OS = 10.08 months, 95% CI 5.23-19.44) and PFS (DC vaccine: median PFS = 11.01 months, 95% CI 5.25-23.09; Peptide vaccine: median PFS = 1.97 months, 95% CI 1.53-2.54) of DC vaccine were also longer than that of peptide vaccine. HBV-related HCC may acquire more benefits from tumor vaccines than HCV-related HCC. In almost all studies, the observed toxicities were moderate even tiny. CONCLUSIONS: Tumor vaccines for HCC, especially DC vaccine, are safe and worth exploring. More high-quality prospective studies are warranted.


Assuntos
Vacinas Anticâncer , Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Vacinas Anticâncer/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Intervalo Livre de Progressão , Análise de Sobrevida
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