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BACKGROUND: Regorafenib (R) and fruquintinib (F) are the standard third-line regimens for colorectal cancer (CRC) according to the National Comprehensive Cancer Network guidelines, but both have limited efficacy. Several phase 2 trials have indicated that R or F combined with immune checkpoint inhibitors can reverse immunosuppression and achieve promising efficacy for microsatellite stable or proficient mismatch repair (MSS/pMMR) CRC. Due to the lack of studies comparing the efficacy between F, R, F plus programmed death-1 (PD-1) inhibitor, and R plus PD-1 inhibitors (RP), it is still unclear whether the combination therapy is more effective than monotherapy. AIM: To provide critical evidence for selecting the appropriate drugs for MSS/pMMR metastatic CRC (mCRC) patients in clinical practice. METHODS: A total of 2639 CRC patients were enrolled from January 2018 to September 2022 in our hospital, and 313 MSS/pMMR mCRC patients were finally included. RESULTS: A total of 313 eligible patients were divided into F (n = 70), R (n = 67), F plus PD-1 inhibitor (FP) (n = 95) and RP (n = 81) groups. The key clinical characteristics were well balanced among the groups. The median progression-free survival (PFS) of the F, R, FP, and RP groups was 3.5 months, 3.6 months, 4.9 months, and 3.0 months, respectively. The median overall survival (OS) was 14.6 months, 15.7 months, 16.7 months, and 14.1 months. The FP regimen had an improved disease control rate (DCR) (P = 0.044) and 6-month PFS (P = 0.014) and exhibited a better trend in PFS (P = 0.057) compared with F, and it was also significantly better in PFS than RP (P = 0.030). RP did not confer a significant survival benefit; instead, the R group had a trend toward greater benefit with OS (P = 0.080) compared with RP. No significant differences were observed between the R and F groups in PFS or OS (P > 0.05). CONCLUSION: FP is superior to F in achieving 6-month PFS and DCR, while RP is not better than R. FP has an improved PFS and 6-month PFS compared with RP, but F and R had similar clinical efficacy. Therefore, FP may be a highly promising strategy in the treatment of MSS/pMMR mCRC.
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Histone post-translational modifications (PTMs), such as acetylation and recently identified lysine 2-hydroxyisobutyrylation (Khib), act as active epigenomic marks in plants. SANT domain-containing proteins SANT1, SANT2, SANT3 and SANT4 (SANT1/2/3/4), derived from PIF/Harbinger transposases, form a complex with HISTONE DEACETYLASE 6 (HDA6) to regulate gene expression via histone deacetylation. However, whether SANT1/2/3/4 coordinate different types of PTMs to regulate transcription and mediate responses to specific stresses in plants remains unclear. Here, in addition to modulating histone deacetylation, we found that SANT1/2/3/4 proteins acted like HDA6 or HDA9 in regulating the removal of histone Khib in Arabidopsis (Arabidopsis thaliana). Histone H3 lysine acetylation (H3KAc) and histone Khib were coordinated by SANT1/2/3/4 to regulate gene expression, with H3KAc playing a predominant role and Khib acting complementarily to H3KAc. SANT1/2/3/4 mutation significantly increased the expression of heat-inducible genes with concurrent change of H3KAc levels under normal and heat stress conditions, resulting in enhanced thermotolerance. This study revealed the critical roles of Harbinger transposon-derived SANT domain-containing proteins in transcriptional regulation by coordinating different types of histone PTMs and in the regulation of plant thermotolerance by mediating histone acetylation modification.
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PURPOSE: It is unclear whether traditional Chinese patent medicines can resist premature aging. This prospective study investigated the effects of Bazi Bushen Capsule (BZBS) which is a traditional Chinese patent medicine for tonifying the kidney essence on premature senility symptoms and quality of life, telomerase activity and telomere length. STUDY DESIGN AND METHODS: It was a parallel, multicenter, double-blind, randomized, and placebo-controlled trial. Subjects (n = 530) aged 30-78 years were randomized to receive BZBS or placebo capsules 12 weeks. The primary outcome was the clinical feature of change in kidney deficiency for aging evaluation scale (CFCKD-AES) and tilburg frailty indicator (TFI). The secondary outcomes were SF-36, serum sex hormone level, five times sit-to-stand time (FTSST), 6MWT, motor function test-grip strength, balance test, walking speed, muscle mass measurement, telomerase and telomere length. RESULTS: After 12 weeks of treatment, the CFCKD-AES and TFI scores in the BZBS group decreased by 13.79 and 1.50 respectively (6.42 and 0.58 in the placebo group, respectively); The SF-36 in the BZBS group increased by 98.38 (23.79 in the placebo group). The FTSST, motor function test grip strength, balance test, walking speed, and muscle mass in the elderly subgroup were all improved in the BZBS group. The telomerase content in the BZBS group increased by 150.04 ng/ml compared to the placebo group. The fever led one patient in the placebo group to discontinue the trial. One patient in the placebo group withdrew from the trial due to pregnancy. None of the serious AEs led to treatment discontinuation, and 3 AEs (1.14%) were assessed as related to BZBS by the primary investigator. CONCLUSIONS: BZBS can improve premature aging symptoms, frailty scores, and quality of life, as well as improve FTSST, motor function: grip strength, balance test, walking speed, and muscle mass in elderly subgroups of patients, and enhance telomerase activity, but it is not significantly associated with increasing telomere length which is important for healthy aging. TRIAL REGISTRY: https://www.chictr.org.cn/showproj.html?proj=166181.
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Envejecimiento Prematuro , Medicamentos Herbarios Chinos , Calidad de Vida , Humanos , Método Doble Ciego , Masculino , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Persona de Mediana Edad , Femenino , Anciano , Envejecimiento Prematuro/tratamiento farmacológico , Adulto , Telomerasa , Fuerza de la Mano , Estudios Prospectivos , Telómero/efectos de los fármacosRESUMEN
Introduction: Pholiota nameko is a widely consumed edible fungus. This study focuses on two crucial developmental stages of Pholiota nameko, namely, mycelium and ascospores. The objectives of this research were to investigate changes in microbial diversity and community structure during the growth of Pholiota nameko and to analyze the adaptability of the dominant strains to their respective habitats through metabolic. Methods: Specifically, we conducted second-generation sequencing of the 16S rRNA gene (Illumina) on samples obtained from these stages. In addition, we isolated and characterized endophytes present in Pholiota nameko, focusing on examining the impact of dominant endophyte genera on autolysis. We also conducted a metabolic pathway analysis. Results and discussion: The results unveiled 578,414 valid sequences of Pholiota nameko endophytic fungi. At the phylum level, the dominant taxa were Basidiomycota, Ascomycota, Zoopagomycota, and Mucoromycota. At the genus level, the dominant taxa observed were Pholiota, Inocybe, Fusarium, and Hortiboletus. For endophytic bacteria, we obtained 458,475 valid sequences. The dominant phyla were Proteobacteria, TM6, Firmicutes, and Bacteroidetes, while the dominant genera were Edaphobacter, Xanthomonas, Burkholderia, and Pseudomonas. Moreover, we identified the isolated strains in Pholiota nameko using 16S rDNA, and most of them were found to belong to the genus Pseudomonas, with Pseudomonas putida being the most prevalent strain. The findings revealed that the Pseudomonas putida strain has the ability to slow down the breakdown of soluble proteins and partially suppress the metabolic processes that generate superoxide anion radicals in Pholiota nameko, thereby reducing autolysis. Additionally, our results demonstrated that molybdenum enzyme-mediated anaerobic oxidative phosphorylation reactions were the primary energy metabolism pathway in the Pseudomonas putida strain. This suggests that the molybdenum cofactor synthesis pathway might be the main mechanism through which Pholiota nameko adapts to its complex and diverse habitats.
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Bile acids (BAs) have surpassed their traditional roles as lipid solubilizers and regulators of BA homeostasis to emerge as important signalling molecules. Recent research has revealed a connection between microbial dysbiosis and metabolism disruption of BAs, which in turn impacts ageing-related diseases. The human BAs pool is primarily composed of primary BAs and their conjugates, with a smaller proportion consisting of secondary BAs. These different BAs exert complex effects on health and ageing-related diseases through several key nuclear receptors, such as farnesoid X receptor and Takeda G protein-coupled receptor 5. However, the underlying molecular mechanisms of these effects are still debated. Therefore, the modulation of signalling pathways by regulating synthesis and composition of BAs represents an interesting and novel direction for potential therapies of ageing-related diseases. This review provides an overview of synthesis and transportion of BAs in the healthy body, emphasizing its dependence on microbial community metabolic capacity. Additionally, the review also explores how ageing and ageing-related diseases affect metabolism and composition of BAs. Understanding BA metabolism network and the impact of their nuclear receptors, such as farnesoid X receptor and G protein-coupled receptor 5 agonists, paves the way for developing therapeutic agents for targeting BA metabolism in various ageing-related diseases, such as metabolic disorder, hepatic injury, cardiovascular disease, renal damage and neurodegenerative disease.
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Envejecimiento , Ácidos y Sales Biliares , Humanos , Ácidos y Sales Biliares/metabolismo , Ácidos y Sales Biliares/biosíntesis , Envejecimiento/metabolismo , Animales , Receptores Citoplasmáticos y Nucleares/metabolismo , Enfermedades Metabólicas/metabolismoRESUMEN
In traditional Chinese medicine, Aurantii Fructus Immatures (AFIs) have been utilized for more than 2000 years. The proportions of different fruit parts are crucial for evaluating AFI quality in China. However, the basis for this statement's substance is unclear. Differences in quality are intimately correlated with a plant's metabolite composition. On the basis of a widely targeted metabolome, this study intended to investigate the metabolite composition and evaluate the antioxidant capacity of the peel and pulp of an AFI. Metabolites were identified and quantified by UHPLC-QqQ-MS. To assess their antioxidant ability, DPPH and ABTS assays were carried out. There were 1327 chemical compounds identified by UHPLC-QqQ-MS. After screening the differential metabolites using a multivariate statistical analysis, it was found that there were 695 significant differences in the metabolites between the peel and the pulp. Among them, it was discovered that the content of active ingredients in the peel group was higher than that in the pulp group. Furthermore, the aqueous extracts from the peel showed stronger antioxidant capacities than those from the pulp. The metabolites and antioxidant capacities were significantly different between the peel and the pulp. This study of different fruit parts might provide a guide for AFI quality assessments.
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Antioxidantes , Frutas , Metabolómica , Antioxidantes/metabolismo , Frutas/química , Frutas/metabolismo , Metabolómica/métodos , Cromatografía Líquida de Alta Presión , Citrus/química , Citrus/metabolismo , Metaboloma , Extractos Vegetales/química , Extractos Vegetales/farmacologíaRESUMEN
BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is the main subtype of esophageal cancer. Current therapeutic effect is far from satisfaction. Hence, identifying susceptible genes and potential targets is necessary for therapy of ESCC patients. METHODS: Plant homeodomain (PHD)-finger domain protein 5 A (PHF5A) expression in ESCC tissues was examined by immunohistochemistry. RNA interference was used for in vitro loss-of-function experiments. In vivo assay was performed using xenograft mice model by subcutaneous injection. Besides, microarray assay and co-immunoprecipitation experiments were used to study the potential downstream molecules of PHF5A in ESCC. The molecular mechanism between PHF5A and vascular endothelial growth factor A (VEGFA) was explored by a series of ubiquitination related assays. RESULTS: We found that PHF5A was highly expressed in ESCC tissues compared to normal tissues and that was correlated with poor prognosis of ESCC. Loss-of-function experiments revealed that PHF5A silence remarkably inhibited cell proliferation, migration, and induced apoptosis as well as cell cycle arrest. Consistently, in vivo assay demonstrated that PHF5A deficiency was able to attenuate tumor growth. Furthermore, molecular studies showed that PHF5A silencing promoted VEGFA ubiquitination by interacting with MDM2, thereby regulating VEGFA protein expression. Subsequently, in rescue experiments, our data suggested that ESCC cell viability and migration promoted by PHF5A were dependent on intact VEGFA. Finally, PI3K/AKT signaling rescue was able to alleviate shPHF5A-mediated cell apoptosis and cell cycle arrest. CONCLUSION: PHF5A is a tumor promoter in ESCC, which is dependent on VEGFA and PI3K/AKT signaling. PHF5A might serve as a potential therapeutic target for ESCC treatment.
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Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Factor A de Crecimiento Endotelial Vascular , Animales , Humanos , Ratones , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patología , Carcinoma de Células Escamosas de Esófago/genética , Carcinoma de Células Escamosas de Esófago/metabolismo , Carcinoma de Células Escamosas de Esófago/patología , Regulación Neoplásica de la Expresión Génica , Fosfatidilinositol 3-Quinasas/genética , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas de Unión al ARN/genética , Transactivadores/genética , Factor A de Crecimiento Endotelial Vascular/genética , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
BACKGROUND: Anlotinib has demonstrated promising anti-tumor efficacy in various solid tumors. Additionally, there is evidence suggesting that immune therapy can enhance the systemic responses of anlotinib. This study aimed to assess the effectiveness and safety of combining anlotinib with PD-1 inhibitors compared to fluoropyrimidine-based chemotherapy as a second-line treatment option for advanced biliary tract cancers (BTCs). METHODS: A total of 242 patients with BTCs were screened at the First Affiliated Hospital of Zhengzhou University from October 2015 to October 2022. Among them, 78 patients who received either anlotinib plus PD-1 inhibitors (AP) or fluoropyrimidine-based chemotherapy (FB) as second-line treatment were included in the study. The primary endpoint was progression-free survival (PFS), and the secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS), safety, and predictive tumor biomarkers. RESULTS: Among the 78 patients with BTCs, 39 patients received AP, while 39 patients were administered FB. The ORR in the AP group was 20.5%, compared to 5.1% in the FB group. The DCR was 87.2% in the AP group and 66.7% in the FB group. The AP group demonstrated significantly better ORR and DCR compared to the FB group (p = 0.042, p = 0.032). The median PFS and OS in the AP group were 7.9 months (95% CI: 4.35-11.45) and 13.9 months (95% CI: 5.39-22.41), respectively. In the FB group, the median PFS and OS were 4.1 months (95% CI: 3.17-5.03) and 13.2 months (95% CI: 8.72-17.68), respectively. The AP group exhibited significantly better median PFS than the FB group (p = 0.027). In the subgroup analysis, patients without liver metastasis had a much longer PFS in the AP group compared to the FB group (14.3 vs. 5.5 months, p = 0.016). Similarly, patients with CEA ≤ 5 µg/L also demonstrated a longer PFS in the AP group compared to the FB group (8.7 vs. 3.9 months, p = 0.008). CONCLUSIONS: The combination of anlotinib and PD-1 inhibitors demonstrated a promising clinical effect compared to fluoropyrimidine-based chemotherapy in the second-line treatment of refractory advanced BTCs. Liver metastases and CEA levels may serve as predictive factors for identifying patients who may benefit from AP therapy.
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Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias del Sistema Biliar , Inhibidores de Puntos de Control Inmunológico , Indoles , Quinolinas , Humanos , Masculino , Femenino , Persona de Mediana Edad , Quinolinas/uso terapéutico , Quinolinas/efectos adversos , Quinolinas/administración & dosificación , Neoplasias del Sistema Biliar/tratamiento farmacológico , Neoplasias del Sistema Biliar/patología , Neoplasias del Sistema Biliar/mortalidad , Anciano , Indoles/uso terapéutico , Indoles/administración & dosificación , Indoles/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Adulto , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Inhibidores de Puntos de Control Inmunológico/administración & dosificación , Supervivencia sin Progresión , Estudios Retrospectivos , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Anciano de 80 o más AñosRESUMEN
Mushroom dietary fiber is a type of bioactive macromolecule derived from the mycelia, fruiting bodies, or sclerotia of edible or medicinal fungi. The use of mushroom dietary fiber as a prebiotic has recently gained significant attention for providing health benefits to the host by promoting the growth of beneficial microorganisms; therefore, mushroom dietary fiber has promising prospects for application in the functional food industry and in drug development. This review summarizes methods for the preparation and modification of mushroom dietary fiber, its degradation and metabolism in the intestine, its impact on the gut microbiota community, and the generation of short-chain fatty acids (SCFAs); this review also systematically summarizes the beneficial effects of mushroom dietary fiber on host health. Overall, this review aims to provide theoretical guidance and a fresh perspective for the prebiotic application of mushroom dietary fiber in the development of new functional foods and drugs.
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Objective: This aim of this study was to investigate the prognostic significance of KIT exon 11 mutation subtypes in patients with GISTs. Methods: A total of 233 consecutive patients diagnosed with GISTs at the First Affiliated Hospital of Zhengzhou University from January 2013 to August 2018 were included in this study. The prevalence and mutation landscape of exon 11 in KIT was presented. The clinicopathological characteristics and prognosis among the different mutation subtypes were analyzed. All the statistical analyses were performed by SPSS22.0. Results: Somatic mutational analysis indicated that point mutations were the most frequently detected mutations followed by deletions & compound mutations and insertion and tandem duplication mutations in the stomach. Point mutations showed a low mitotic count and a high risk of recurrence, and deletions and compound mutations have a high mitotic count while insertions and tandem duplication mutations showed a low mitotic count with an intermediate recurrence risk. Point mutations and deletions frequently occurred in sequence region codons 550-560 of exon 11, while compound mutations, insertion, and tandem duplication were mainly detected in codons 557-559, 572-580, and 577-581, respectively. The multi-variation analysis demonstrated that tumor diameter and high recurrence risk groups had worse prognostic values. However, mutation types were not significant predictors of relapse-free survival (RFS) in GISTs. Survival analysis suggested no significant difference in RFS between the 557/558 deletion and the other deletions. Conclusion: This study suggested that mutations in exon 11 of the KIT gene were common with intermediate/high recurrence risk in GISTs patients. Tumor diameter ≥5 cm, and deletions mutations might predict a worse prognosis.
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This study aims to analyze the outcomes and measurements of randomized controlled trial(RCT) for traditional Chinese medicine(TCM) treatment of endometriosis(EM) and provide a basis for the building of the core outcome set(COS) of EM. The RCT for TCM treatment of EM was retrieved from medical literature databases with the time interval from inception to February 3, 2022. The Cochrane risk of bias assessment tool was employed to evaluate the risk of bias of the included RCT, and descriptive analyses of the extracted information were carried out. A total of 519 RCTs were included, with the sample sizes ranging from 28-582 patients and 239 outcome indicators(8 outcome indicators per RCT on average). According to the functional properties, the reported outcome indicators were classified into 7 indicators: clinical efficacy assessment, indicators of clinical symptoms and signs, TCM symptom efficacy indicators, physical and chemical examinations, quality of life, long-term prognosis, and safety events. All the 519 RCTs had problems, such as the lack of differentiation between primary and secondary outcome indicators(1.73% RCTs reported such differen-tiation), poor quality, confused criteria for composite outcome indicators and arbitrary combination of indicators(45 criteria for the single outcome indicator of efficiency), and messy measurements(as many as 18 measurements for TCM symptom score). In addition, as a chronic disease, EM requires long-term management. The outcome indicators vary for the patients in different disease stages, such as EM pain, EM infertility, and post-operative EM, while the specific outcome indicator sets for different EM populations remain to be developed. In addition, the time point of measurement for EM long-term outcomes remains unclear, and the definition of TCM syndromes lacks standards. The RCT for TCM treatment had a variety of problems, such as the lack of differentiation of outcome indicators, confusion in criteria and measurements, lack of specific outcome indicator sets for different EM populations, and unclear time points for long-term outcomes. Therefore, the studies about COS need to be carried out urgently.
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Medicamentos Herbarios Chinos , Endometriosis , Femenino , Humanos , Medicina Tradicional China , Endometriosis/diagnóstico , Endometriosis/tratamiento farmacológico , Endometriosis/complicaciones , Calidad de Vida , Síndrome , Medicamentos Herbarios Chinos/efectos adversosRESUMEN
BACKGROUND: Immune inflammatory responses play an important role in spinal cord injury (SCI); however, the beneficial and detrimental effects remain controversial. Many studies have described the role of neutrophils, macrophages, and T lymphocytes in immune inflammatory responses after SCI, although little is known about the role of B lymphocytes, and immunosuppression can easily occur after SCI. METHODS: A mouse model of SCI was established, and HE staining and Nissl staining were performed to observe the pathological changes. The size and morphology of the spleen were examined, and the effects of SCI on spleen function and B cell levels were detected by flow cytometry and ELISA. To explore the specific mechanism of immunosuppression after SCI, B cells from the spleens of SCI model mice were isolated using magnetic beads and analyzed by 4D label-free quantitative proteomics. The level of inflammatory cytokines and iron ions were measured, and the expression of proteins related to the Tom20 pathway was quantified by western blotting. To clarify the relationship between iron ions and B cell pyroptosis after SCI, we used FeSO4 and CCCP, which induce oxidative stress to stimulate SCI, to interfere with B cell processes. siRNA transfection to knock down Tom20 (Tom20-KD) in B cells and human B lymphocytoma cell was used to verify the key role of Tom20. To further explore the effect of iron ions on SCI, we used deferoxamine (DFO) and iron dextran (ID) to interfere with SCI processes in mice. The level of iron ions in splenic B cells and the expression of proteins related to the Tom20-Bax-caspase-gasdermin E (GSDME) pathway were analyzed. RESULTS: SCI could damage spleen function and lead to a decrease in B cell levels; SCI upregulated the expression of Tom20 protein in the mitochondria of B cells; SCI could regulate the concentration of iron ions and activate the Tom20-Bax-caspase-GSDME pathway to induce B cell pyroptosis. Iron ions aggravated CCCP-induced B cell pyroptosis and human B lymphocytoma pyroptosis by activating the Tom20-Bax-caspase-GSDME pathway. DFO could reduce inflammation and promote repair after SCI by inhibiting Tom20-Bax-caspase-GSDME-induced B cell pyroptosis. CONCLUSIONS: Iron overload activates the Tom20-Bax-caspase-GSDME pathway after SCI, induces B cell pyroptosis, promotes inflammation, and aggravates the changes caused by SCI. This may represent a novel mechanism through which the immune inflammatory response is induced after SCI and may provide a new key target for the treatment of SCI.
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Seudolinfoma , Traumatismos de la Médula Espinal , Animales , Humanos , Ratones , Linfocitos B , Proteína X Asociada a bcl-2 , Carbonil Cianuro m-Clorofenil Hidrazona , Caspasas , Gasderminas , Inflamación/etiología , Hierro , PiroptosisRESUMEN
Background: Circular RNAs (circRNAs) are types of endogenous noncoding RNAs produced by selective splicing that are expressed highly specifically in various organisms and tissues and have numerous clinical implications in the regulation of cancer development and progression. Since circRNA is resistant to digestion by ribonucleases and has a long half-life, there is increasing evidence that circRNA can be used as an ideal candidate biomarker for the early diagnosis and prognosis of tumors. In this study, we aimed to reveal the diagnostic and prognostic value of circRNA in human pancreatic cancer (PC). Methods: A systematic search for publications from inception to 22 July 2022 was conducted on Embase, PubMed, Web of Science (WOS), and the Cochrane Library databases. Available studies that correlated circRNA expression in tissue or serum with the clinicopathological, diagnostic, and prognostic values of PC patients were enrolled. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were used to evaluate clinical pathological characteristics. Area under the curve (AUC), sensitivity, and specificity were adopted to assess diagnostic value. Hazard ratios (HRs) were utilized to assess disease-free survival (DFS) and overall survival (OS). Results: This meta-analysis enrolled 32 eligible studies, including six on diagnosis and 21 on prognosis, which accounted for 2,396 cases from 245 references. For clinical parameters, high expression of carcinogenic circRNA was significantly associated with degree of differentiation (OR = 1.85, 95% CI = 1.47-2.34), TNM stage (OR = 0.46, 95% CI = 0.35-0.62), lymph node metastasis (OR = 0.39, 95% CI = 0.32-0.48), and distant metastasis (OR = 0.26, 95% CI = 0.13-0.51). As for clinical diagnostic utility, circRNA could discriminate patients with pancreatic cancer from controls, with an AUC of 0.86 (95% CI: 0.82-0.88), a relatively high sensitivity of 84%, and a specificity of 80% in tissue. In terms of prognostic significance, carcinogenic circRNA was correlated with poor OS (HR = 2.00, 95% CI: 1.76-2.26) and DFS (HR = 1.96, 95% CI: 1.47-2.62). Conclusion: In summary, this study demonstrated that circRNA may act as a significant diagnostic and prognostic biomarker for pancreatic cancer.
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KEY MESSAGE: We developed a new method phenotypic recombination BSA/BSR (PR-BSA/BSR), which could simultaneously identify the candidate genomic regions associated with two traits in a segregating population. Bulked segregant analysis sequencing (BSA-seq) has been widely used for identifying the genomic regions affecting a certain trait. In this study, we developed a modified BSA/bulked segregant RNA-sequencing (BSR-seq) method, which we named phenotypic recombination BSA/BSR (PR-BSA/BSR), to simultaneously identify candidate genomic regions associated with two traits in a segregating population. Lateral branch angle (LBA) and flower-branch pattern (FBP) are two important traits associated with the peanut plant architecture because they affect the planting density and light use efficiency. We generated an F6 population (with two segregating traits) derived from a cross between the inbred lines Pingdu9616 (erect and sequential; ES-type) and Florunner (spreading and alternating; SA-type). The selection of bulks with extreme phenotypes was a key step in this study. Specifically, 30 individuals with recombinant phenotypes [i.e., spreading and sequential (SS-type) and erect and alternating (EA-type)] were selected to generate two bulks. The transcriptomes of individuals were sequenced and then the loci related to LBA and FBP were simultaneously detected via a ΔSNP-index strategy, which involved the direction of positive and negative peaks in the ∆SNP-index plot. The LBA-related locus was mapped to a 6.82 Mb region (101,743,223-108,564,267 bp) on chromosome 15, whereas the FBP-related locus was mapped to a 2.16 Mb region (117,682,534-119,846,824 bp) on chromosome 12. Furthermore, the marker-based classical QTL mapping method was used to analyze the PF-F6 population, which confirmed our PR-BSA/BSR results. Therefore, the PR-BSA/BSR method produces accurate and reliable data.
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Arachis , Sitios de Carácter Cuantitativo , Arachis/genética , Mapeo Cromosómico , Fenotipo , Recombinación GenéticaRESUMEN
Molybdenum carbide is one of non-precious metal materials and it is a promising electrocatalyst for hydrogen production. Synthesis and improvement of molybdenum carbide's catalytic performance is of great significance. Herein, carbon-based Mo2 C with hybrid phase of MoO2 was fabricated by matching the composition of Mo and C derived from pomelo peel and optimizing raw carbon amount and prolysis temperature. The resulting MoO2 /Mo2 C@C is composed of loose microspheres with mesoporous microstructure and is self-assembled from nanoparticles. The results show that MoO2 /Mo2 C@C2 material exhibits excellent HER performance and only a low overpotentials of 143â mV is needed to drive the current density of 10â mA cm-2 in alkaline solution, and Tafel slopes are only 63.4â mV dec-1 , respectively. Notably, it has potential application at low overpotentials to drive large current density and this strategy also provides a universal route to prepare non-noble metal catalyst with hybrid phase of oxide/carbide.
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Carbono , Molibdeno , Óxidos , HidrógenoRESUMEN
We herein describe a palladium-catalyzed hydrocyanation of propiolamides for the stereodivergent synthesis of trisubstituted acrylonitriles. This synthetic method tolerated various primary, secondary and tertiary propiolamides. The cautious selection of a suitable ligand is essential to the success of this stereodivergent process. Control experiments indicate the intermediacy of E-acrylonitriles, which lead to Z-acrylonitriles via isomerization. The density functional theory calculations suggests that the bidentate ligand L2 enables a feasible cyclometallation/isomerization pathway for the E to Z isomerization, while the monodentate ligand L1 inhibits the isomerization, leading to divergent stereoselectivity. The usefulness of this method can be demonstrated by the readily derivatization of products to give various E- and Z-trisubstituted alkenes. In addition, the E- and Z-acrylonitrile products have also been successfully employed in cycloaddition reactions.
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Acrilonitrilo , Paladio , Estereoisomerismo , Ligandos , CatálisisRESUMEN
OBJECTIVE: To analyze the factors related to pregnancy of endometriosis and whether Chinese herbal medicines (CHMs) can improve pregnancy outcomes in patients with endometriosis in long-term management. METHODS: This multicenter cohort study retrospectively analyzed the clinical data of endometriosis patients with fertility needs from January 2019 to November 2019. A total of 252 patients with endometriosis from 5 level-III Grade A hospitals in Beijing were included in this study. Univariate and multivariate logistic regression analysis were performed for the relevant factors. The propensity score matching (PSM) function of SPSS software was used to match the CHMs group with the non-CHMs group. The pregnancy rate and live birth rate were analyzed. RESULTS: The results of univariate analysis showed that age, disease course, presence of infertility, presence of adenomyosis, time after surgery or use of gonadotropin-releasing hormone agonist (GnRH-a), use of CHMs and follow-up time were influencing factors of pregnancy in endometriosis patients (P<0.05). The results of multivariate analysis showed that age, presence of adenomyosis, time after surgery or use of GnRH-a, use of CHMs and follow-up time were independent factors affecting pregnancy in endometriosis patients, among which, age ⩾35 years old, presence of adenomyosis and follow-up time >6 months were independent risk factors (OR=0.445, 0.348, 0.140, respectively, P<0.05), time after surgery or use of GnRH-a ⩽6 months and use of CHMs were independent protective factors (OR=3.839, 3.842, respectively, P<0.05). After PSM, 99 pairs of two groups were matched successfully. The pregnancy rate of the CHMs group was higher than that of the non-CHMs group [55.56% (55/99) vs. 36.36% (36/99), P<0.05]. The live birth rate of the CHMs group was higher than that of the non-CHMs group [49.49% (49/99) vs. 35.35% (35/99), P<0.05]. CONCLUSION: CHMs can effectively improve clinical pregnancy rate and live birth rate of patients with endometriosis in the chronic disease management.
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Adenomiosis , Endometriosis , Embarazo , Femenino , Humanos , Adulto , Resultado del Embarazo , Endometriosis/complicaciones , Endometriosis/tratamiento farmacológico , Endometriosis/cirugía , Estudios Retrospectivos , Estudios de Cohortes , Hormona Liberadora de Gonadotropina , Extractos Vegetales , Fertilización In VitroRESUMEN
Current medical treatments for endometriosis-associated pain (EAP) have limitations, including symptom recurrence and hormonal side effects. For this reason, it is important to elucidate any alternative or complementary treatments available, while Chinese herbal medicine (CHM) shows potential to be this treatment. This study aims to provide evidence for the efficacy and safety of CHM for EAP. Randomized control trials comparing CHM to other treatments for EAP in women with endometriosis were considered eligible, and they were searched for in Medline, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov, as well as in the Chinese databases Sino-Med and CNKI, from inception to October 2021. Numerous outcomes were put through meta-analysis using a weighted mean difference and a 95% CI, and the results of dichotomous data were presented as a pooled RR with a 95% CI. A total of 34 eligible studies with 3389 participants were included. Compared with no treatment, there was a statistically significant pooled benefit of CHM on dysmenorrhea at the end of 3-month treatment, and these effects continued for 3 months, but not 9 months, after treatment. Compared with conventional therapy, a significant difference was found in the levels of pelvic pain with a lower rate of hot flush and irregular vaginal bleeding at the end of treatment for 3 months, but not after treatment. Comparing combined treatment with CHM and conventional therapy with conventional therapy alone, significant decreases were found in dysmenorrhea, dyspareunia, and pelvic pain after a 3-month treatment cycle, and in dysmenorrhea after a 4-month treatment cycle with a lower hot flash rate. In conclusion, CHM, used alone or in combination with conventional therapies, appears to have benefits in relieving EAP with fewer side effects than traditional treatment.
Asunto(s)
Medicamentos Herbarios Chinos , Endometriosis , Femenino , Humanos , Endometriosis/complicaciones , Endometriosis/tratamiento farmacológico , Dismenorrea/tratamiento farmacológico , Dismenorrea/etiología , Dolor Pélvico/tratamiento farmacológico , Dolor Pélvico/etiología , Terapia CombinadaRESUMEN
PURPOSE: Exploring the status and related factors of postoperative recurrence of ovarian endometriosis. METHODS: This study analyzed the results of questionnaires conducted in 27 hospitals across the country from January 2019 to November 2021. All women were divided into recurrence group and non-recurrence group to analyze the recurrence rate and related factors after ovarian endometriosis surgery. RESULTS: The recurrence rates of ovarian endometriosis within 1 year, 1-2 years, 2-3 years, 3-4 years, 4-5 years and more than 5 years were 6.27%, 35.85%, 55.38%, 65.00% and 56.82%, respectively. Significant differences were found between two groups in terms of age at surgery (OR: 0.342, 95%CI: 0.244-0.481, P < 0.001), presence of dysmenorrhea (OR: 1.758, 95%CI: 1.337-2.312, P < 0.001), presence of adenomyosis (OR: 1.948, 95%CI: 1.417-2.678, P < 0.001) and family history of endometriosis or adenomyosis (OR: 1.678, 95%CI: 1.035-2.721, P = 0.021). The age at surgery (OR: 0.358, 95%CI: 0.253-0.506, P < 0.001), presence of dysmenorrhea (OR: 1.379, 95%CI: 1.026-1.853, P = 0.033) and presence of adenomyosis (OR: 1.799, 95%CI: 1.275-2.537, P = 0.001) were significantly associated with endometrioma recurrence in multivariate analysis. No significant associations were found between the recurrence rate and body mass index (BMI), educational background, age of menarche, gravida, parity, uterine leiomyoma, endometrial polyps or postoperative use of gonadotropin-releasing hormone agonist (GnRH-a). CONCLUSIONS: Dysmenorrhea and presence of adenomyosis are independent risk factors for postoperative recurrence of ovarian endometriosis, and older age is an independent protective factor for postoperative recurrence.