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Background: Non-cystic fibrosis bronchiectasis is associated with airway pathogen colonization. We planned to investigate the inflammatory markers in patients with different airway pathogens and their correlation with disease severity. Methods: We enrolled patients aged between 20 and 75 from October 2021 to August 2022. All patients had sputum evaluation for bacterial and fungal cultures before enrollment, and were classified into four groups according to the culture results. Results: Forty-four patients with non-CF bronchiectasis and six controls were enrolled and categorized as follows: Group 1, no pathogens identified in sputum cultures (n = 14); Group 2, positive fungal culture results (n = 18); Group 3, positive P. aeruginosa culture results (n = 7); and Group 4, positive culture results for both fungi and P. aeruginosa (n = 5). Group 4 had significantly higher serum defensin α1, IL-6 and tissue inhibitors of MMP (TIMP)-1 levels than group 1 patients. The serum levels of IL-6 and TIMP-1 were positively correlated with the FACED score and negatively correlated with distance-saturation product. Conclusion: Significantly higher levels of serum IL-6 and TIMP-1 were found in the patients who had concomitant fungal and P. aeruginosa colonization, and were closely related to clinical severity and may have important roles in disease monitoring.
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BACKGROUND: Persistent infection with high-risk human papillomavirus (HR-HPV) plays a key role in the onset of cervical cancer. This study was designed to examine the epidemiological trends and genotype distribution of HPV from 2014 to 2023 in the plateau region of Southwest China. METHODS: The findings could offer valuable insights for clinical screening of cervical cancer and the formulation of HPV vaccination policies. This retrospective study analyzed 66,000 women who received HPV-DNA testing at the First People's Hospital of Qujing, Yunnan, China, between 2014 and 2023. The cohort consisted of 33,512 outpatients, 3,816 inpatients, and 28,672 individuals undergoing health examinations. Cervical cells were collected for DNA extraction, and PCR amplification along with Luminex xMAP technology were used to detect 27 HPV genotypes. The data analysis was conducted using GraphPad Prism and IBM SPSS Statistics 27 software. RESULTS: The overall HPV infection rate at the First People's Hospital of Qujing declined from 24.92% in 2014 to 16.29% in 2023, averaging 16.02%. Specific infection rates were 18.50% among outpatients, 12.97% among inpatients, and 13.53% for health examination attendees. The predominant high-risk HPV genotypes identified were HPV52 (2.61%), HPV16 (2.06%), HPV58 (1.81%), HPV53 (1.55%), and HPV39 (1.09%). Meanwhile, the most frequent low-risk HPV genotypes were HPV6 (1.30%), HPV61 (1.21%), and HPV11 (0.85%). In HPV-positive cases, the distribution of single, double, triple, and quadruple or more infections were 79.90%, 15.17%, 3.59%, and 1.33%, respectively. The proportions of pure LR-HPV, pure HR-HPV, and mixed infections were 22.16%, 67.82%, and 10.02%, respectively. Age-specific analysis revealed a bimodal distribution of HPV infection, with the infection rate rapidly decreasing from 44.02% in the ≤ 19 age group to 19.55% in the 20-29 age group and 13.84% in the 30-39 age group, followed by a gradual increase to 14.64% in the 40-49 age group, 16.65% in the 50-59 age group, and 22.98% in the ≥ 60 age group. The coverage rates of the three available vaccines are all below 50%. The results of this study indicated a declining trend in HPV prevalence in the plateau region of Southwest China over the period from 2014 to 2023, especially in the reduction of genotypes targeted by vaccines. CONCLUSION: There were significant variations in the genotypes prevalent among different age groups, years, and patient sources within the same region. The underwhelming vaccination rates emphasize the critical need for developing either a multivalent vaccine or a personalized vaccine that targets the HPV genotypes common in the Chinese population. Furthermore, vaccinating adolescents to curb HPV infection and ensuring regular cervical cancer screenings for postmenopausal women are crucial steps.
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Genotipo , Papillomaviridae , Infecciones por Papillomavirus , Humanos , Femenino , Infecciones por Papillomavirus/epidemiología , Infecciones por Papillomavirus/virología , China/epidemiología , Adulto , Prevalencia , Persona de Mediana Edad , Estudios Retrospectivos , Adulto Joven , Papillomaviridae/genética , Papillomaviridae/clasificación , Papillomaviridae/aislamiento & purificación , Adolescente , Anciano , Neoplasias del Cuello Uterino/virología , Neoplasias del Cuello Uterino/epidemiología , ADN Viral/genética , Cuello del Útero/virologíaRESUMEN
There is significant value in developing multifunctional drug delivery systems with high therapeutic efficiency for diagnosing and treating tumors. In this study, we synthesized the ATP-triggered and pH-sensitive material ZIF-90 using the liquid-phase diffusion method. This was done to load 10-hydroxycamptothecin (HCPT), and the FA-PEG-NH2 conjugate was synthesized through an amidation reaction. We further modified the HCPT@ZIF-90 nanocomposite by employing the Schiff base reaction to create the HCPT@ZIF-90-PEG-FA nanomaterial. Drug loading test results revealed a high HCPT drug loading of up to 22.3% by weight. In the drug release experiment, the cumulative drug release of HCPT@ZIF-90 nanomaterials in pH 5.4 and ATP solutions was the highest after 72 hours. The active targeted delivery of FA and the dual-responsive release of HCPT by ZIF-90 significantly enhanced the therapeutic effect of HCPT@ZIF-90-PEG-FA on human colon cancer cells (HCT116). In the cytotoxicity test, when 100 µg mL-1 of HCPT@ZIF-90-PEG-FA was incubated with cells, the cell survival rate was 16.61 ± 1.19%, significantly lower than that of the other experimental groups. This result indicates that HCPT@ZIF-90-PEG-FA exhibits excellent anti-tumor activity. Cell cycle experiments have shown that HCPT@ZIF-90-PEG-FA may inhibit the proliferation of cancer cells by blocking DNA synthesis and halting cell cycle progression. Cell uptake experiments showed that HCPT@ZIF-90-PEG-FA was mainly present in the cytoplasm of HCT1116 cells, indicating successful cellular entry of the drug to exert its therapeutic effect. In vivo experiments also demonstrated that HCPT@ZIF-90-PEG-FA nanomaterials can effectively eradicate HCT116 tumors. The utilization of the nano-drug carrier ZIF-90, along with the modification with PEG-FA, notably improved the therapeutic efficacy of HCPT. These results suggest that the system, with its active targeted delivery of FA and dual-responsive release of HCPT, could present a novel strategy for treating human colorectal cancer.
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Pentavalent rotavirus vaccine (RV5) coverage and changes in rotavirus detection in the prevaccine and postvaccine era in Chengdu were investigated. The results showed that the coverage of RV5 had been increasing but still relatively low. Nevertheless, the dramatical decline in the rotavirus detection was observed after the introduction of RV5. Efforts to improve the coverage of rotavirus vaccination should continue to maximize the public health benefits.
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RNA-binding proteins (RBPs) are a class of proteins that primarily function by interacting with different types of RNAs and play a critical role in regulating the transcription and translation of cancer-related genes. However, their role in the progression of hepatocellular carcinoma (HCC) remains unclear. In this study, we analyzed RNA sequencing data and the corresponding clinical information of patients with HCC to screen for prognostic RBPs. Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) was identified as an independent prognostic factor for liver cancer. It is upregulated in HCC and is associated with a poor prognosis. Elevated IGF2BP3 expression was validated via immunohistochemical analysis using a tissue microarray of patients with HCC. IGF2BP3 knockdown inhibited the proliferation of Hep3B and HepG2 cells, whereas IGF2BP3 overexpression promoted the expansion of HuH-7 and MHCC97H cells. Mechanistically, IGF2BP3 modulates cell proliferation by regulating E2F1 expression. DNA hypomethylation of the IGF2BP3 gene may increase the expression of IGF2BP3, thereby enhancing cell proliferation in HCC. Therefore, IGF2BP3 may act as a novel prognostic biomarker and a potential therapeutic target for HCC.
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Carcinoma Hepatocelular , Proliferación Celular , Metilación de ADN , Factor de Transcripción E2F1 , Epigénesis Genética , Regulación Neoplásica de la Expresión Génica , Neoplasias Hepáticas , Proteínas de Unión al ARN , Regulación hacia Arriba , Humanos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/metabolismo , Proliferación Celular/genética , Proteínas de Unión al ARN/genética , Proteínas de Unión al ARN/metabolismo , Factor de Transcripción E2F1/metabolismo , Factor de Transcripción E2F1/genética , Masculino , Regulación hacia Arriba/genética , Femenino , Pronóstico , Línea Celular Tumoral , Persona de Mediana Edad , Células Hep G2 , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismoRESUMEN
Triple-negative breast cancer (TNBC) is a highly lethal malignancy, and its clinical management encounters severe challenges due to its high metastatic propensity and the absence of effective therapeutic targets. To improve druggability of aurovertin B (AVB), a natural polyketide with a significant antiproliferative effect on TNBC, a series of NO donor/AVB hybrids were synthesized and tested for bioactivities. Among them, compound 4d significantly inhibited the proliferation and metastasis of TNBC in vitro and in vivo with better safety than that of AVB. The structure-activity relationship analysis suggested that the types of NO donor and the linkers had considerable effects on the activities. Mechanistic investigations unveiled that 4d induced apoptosis and ferroptosis by the reduction of mitochondrial membrane potential and the down-regulation of GPX4, respectively. The antimetastatic effect of 4d was associated with the upregulation of DUSP1. Overall, these compelling results underscore the tremendous potential of 4d for treating TNBC.
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Antineoplásicos , Apoptosis , Ferroptosis , Donantes de Óxido Nítrico , Neoplasias de la Mama Triple Negativas , Animales , Femenino , Humanos , Ratones , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/síntesis química , Antineoplásicos/uso terapéutico , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Descubrimiento de Drogas , Ensayos de Selección de Medicamentos Antitumorales , Ferroptosis/efectos de los fármacos , Ratones Endogámicos BALB C , Ratones Desnudos , Estructura Molecular , Donantes de Óxido Nítrico/farmacología , Donantes de Óxido Nítrico/química , Donantes de Óxido Nítrico/uso terapéutico , Donantes de Óxido Nítrico/síntesis química , Relación Estructura-Actividad , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/patología , Neoplasias de la Mama Triple Negativas/metabolismo , Oxadiazoles/química , Oxadiazoles/farmacología , Piranos/química , Piranos/farmacologíaRESUMEN
BACKGROUND: Due to cardiotoxicity concerns, the concurrent use of epirubicin and trastuzumab has not been fully studied. This study aimed to examine the cardiotoxicity and pathological complete response (pCR) rate associated with the concurrent regimens in patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer (EBC). METHODS: We conducted a systematic search for relevant literature in the NCBI/PubMed, the Cochrane database, and international conference abstracts for phase II or III randomized controlled trials between January 1, 2000, and February 28, 2021, focusing on the concurrent regimens in patients with HER2-positive EBC. To compare the risk of cardiotoxicity and the odds of the pCR rate, we performed linear meta-regression analyses to investigate the effects of multiple covariates. RESULTS: We analyzed 7 neoadjuvant trials involving the concurrent use of epirubicin and trastuzumab with 1797 patients. The median cumulative dose of epirubicin used was 300 mg/m2, with a total of 96 reported adverse cardiac events. The concurrent regimens did not result in a significant increase in cardiotoxicity compared to nonconcurrent regimens (risk ratio [RR] = 1.18, 95% confidence interval [CI] = 0.68-2.05). Compared with nonconcurrent or non-anthracycline-containing regimens, concurrent regimens were associated with a significant increase in the pCR rate (odds ratio = 1.48, 95% CI = 1.04-2.12). The linear fixed-effects meta-regression analysis indicated that in trials including more patients with hormone receptor-positive EBC, the RR of cardiotoxicity significantly increased with concurrent regimens, and the pCR rate became less significant. CONCLUSIONS: The combination of trastuzumab and a low dose of epirubicin positively impacted the pCR rate without a significant increase in cardiotoxicity. We recommend exploring concurrent regimens for HR-negative, HER2-positive tumors to enhance pCR rates, with caution advised for HR-positive tumors due to potential cardiotoxicity.
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Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias de la Mama , Cardiotoxicidad , Epirrubicina , Receptor ErbB-2 , Trastuzumab , Humanos , Epirrubicina/efectos adversos , Epirrubicina/administración & dosificación , Trastuzumab/efectos adversos , Trastuzumab/administración & dosificación , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Neoplasias de la Mama/metabolismo , Femenino , Receptor ErbB-2/metabolismo , Cardiotoxicidad/etiología , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Terapia Neoadyuvante/efectos adversos , Terapia Neoadyuvante/métodos , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del TratamientoRESUMEN
The discovery of effective and safe antiobesity agents remains a challenging yet promising field. Our previous studies identified Bouchardatine derivatives as potential antiobesity agents. However, the 8a-aldehyde moiety rendered them unsuitable for drug development. In this study, we designed two series of novel derivatives to modify this structural feature. Through a structure-activity relationship study, we elucidated the role of the 8a-aldehyde group in toxicity induction. We identified compound 14d, featuring an 8a-N-acylhydrazone moiety, which exhibited significant lipid-lowering activity and reduced toxicity. Compound 14d shares a similar lipid-lowering mechanism with our lead compound 3, but demonstrates improved pharmacokinetic properties and safety profile. Both oral and injectable administration of 14d significantly reduced body weight gain and ameliorated metabolic syndrome in diet-induced obese mice. Our findings identify 14d as a promising antiobesity agent and highlight the potential of substituting the aldehyde group with an N-acylhydrazone to enhance drug-like properties.
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Aldehídos , Fármacos Antiobesidad , Hidrazonas , Obesidad , Animales , Fármacos Antiobesidad/farmacología , Fármacos Antiobesidad/síntesis química , Fármacos Antiobesidad/farmacocinética , Fármacos Antiobesidad/uso terapéutico , Fármacos Antiobesidad/química , Hidrazonas/farmacología , Hidrazonas/química , Hidrazonas/síntesis química , Hidrazonas/farmacocinética , Hidrazonas/uso terapéutico , Ratones , Relación Estructura-Actividad , Aldehídos/química , Masculino , Obesidad/tratamiento farmacológico , Ratones Endogámicos C57BL , Dieta Alta en Grasa/efectos adversos , Humanos , Ratones Obesos , Estructura MolecularRESUMEN
DUSP22 rearrangements are genetic alterations observed in a subset of systemic anaplastic large cell lymphoma (S-ALCL), primary cutaneous anaplastic large cell lymphoma (C-ALCL), and lymphomatoid papulosis (LyP). Previous investigations have shown that the LEF1+/TIA1- immunoprofile and MSC E116K mutations are highly associated with DUSP22 rearrangement in ALCL. However, the existing literature primarily focuses on S-ALCL. Our understanding of the LEF1/TIA1 immunoprofile and MSC mutation status in C-ALCL/LyP is still limited. In this study, we aimed to assess LEF1/TIA1 expression and MSC mutations in a cohort of 23 C-ALCL/LyP cases, along with a control group of histological mimickers. DUSP22 rearrangements were detected by fluorescence in situ hybridization in eight cases (6/10 C-ALCL, 2/13 LyP). We found LEF1 expression in five out of eight (63%) DUSP22-rearranged cases (3/6 C-ALCL, 2/2 LyP), and none of the 15 cases lacking DUSP22 rearrangements. Furthermore, we also found frequent LEF1 expression in adult T-cell leukemia/lymphoma (ATLL; 10 of 11, 91%) within the control group. TIA1 expression was consistently negative in all DUSP22-rearranged C-ALCL/LyP and ATLL cases tested. MCS E116K mutation was identified in one of five DUSP22-rearranged C-ALCL cases. RNA sequencing of a DUSP22-rearranged C-ALCL revealed a novel DUSP22::SNHG fusion coexisting with a CD58::WNT2B fusion. In conclusion, our findings demonstrated a lower rate of LEF1 expression in DUSP22-rearranged C-ALCL/LyP compared to previous reports that predominantly focused on S-ALCL. Moreover, we observed that the majority of ATLL cases also expressed LEF1, suggesting that the LEF1+/TIA1- immunoprofile does not differentiate DUSP22-rearranged C-ALCL/LyP from ATLL.
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Fosfatasas de Especificidad Dual , Reordenamiento Génico , Inmunofenotipificación , Factor de Unión 1 al Potenciador Linfoide , Fosfatasas de la Proteína Quinasa Activada por Mitógenos , Neoplasias Cutáneas , Humanos , Fosfatasas de Especificidad Dual/genética , Fosfatasas de la Proteína Quinasa Activada por Mitógenos/genética , Masculino , Femenino , Persona de Mediana Edad , Factor de Unión 1 al Potenciador Linfoide/genética , Factor de Unión 1 al Potenciador Linfoide/análisis , Adulto , Anciano , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/patología , Antígeno Ki-1/genética , Antígeno Ki-1/análisis , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/análisis , Anciano de 80 o más Años , Hibridación Fluorescente in Situ , Mutación , Papulosis Linfomatoide/genética , Papulosis Linfomatoide/patología , Adulto Joven , Fenotipo , Linfoma Anaplásico Cutáneo Primario de Células Grandes/genética , Linfoma Anaplásico Cutáneo Primario de Células Grandes/patología , Inmunohistoquímica , Linfoma Anaplásico de Células Grandes/genética , Linfoma Anaplásico de Células Grandes/patología , Linfoma Anaplásico de Células Grandes/inmunologíaRESUMEN
BACKGROUND: Complex and high-risk surgical complications pose pressing challenges in the clinical implementation and advancement of endoscopic full-thickness resection (EFTR). Successful perforation repair under endoscopy, thereby avoiding surgical intervention and postoperative complications such as peritonitis, are pivotal for effective EFTR. AIM: To investigate the effectiveness and safety of EFTR assisted by distal serosal inversion under floss traction in gastric submucosal tumors. METHODS: A retrospective analysis of patients with gastric and duodenal submucosal tumors treated with EFTR assisted by the distal serosa inversion under dental floss traction from January 2023 to January 2024 was conducted. The total operation time, tumor dissection time, wound closure time, intraoperative bleeding volume, length of hospital stay and incidence of complications were analyzed. RESULTS: There were 93 patients, aged 55.1 ± 12.1 years. Complete tumor resection was achieved in all cases, resulting in a 100% success rate. The average total operation time was 67.4 ± 27.0 min, with tumor dissection taking 43.6 ± 20.4 min. Wound closure times varied, with gastric body closure time of 24.5 ± 14.1 min and gastric fundus closure time of 16.6 ± 8.7 min, showing a significant difference (P < 0.05). Intraoperative blood loss was 2.3 ± 4.0 mL, and average length of hospital stay was 5.7 ± 1.9 d. There was no secondary perforation after suturing in all cases. The incidence of delayed bleeding was 2.2%, and the incidence of abdominal infection was 3.2%. No patient required other surgical intervention during and after the operation. CONCLUSION: Distal serosal inversion under dental-floss-assisted EFTR significantly reduced wound closure time and intraoperative blood loss, making it a viable approach for gastric submucosal tumors.
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Organic fertilizer substitution has been promoted as a weight loss, efficient, and diversified fertilizer substitution technology in agricultural production. However, there is a lack of comprehensive assessment of the impact of organic fertilizers on N2O and NO emissions from orchards. In this study, N2O and NO emissions from peach orchards were observed annually using static dark box-gas chromatography to compare the effects of chemical fertilizer application alone and partial replacement of chemical fertilizer treatment on NO emissions from peach orchards. The results showed that the partial replacement of chemical fertilizers with organic fertilizers reduced the total N2O and NO emissions from peach orchards by 15.0 % and 9.4 %, respectively. The N2O and NO emission factors were reduced by 21.3 % and 21.1 %. The mineral N content of the soil in the organic fertilizer treatment was lower than that in the chemical fertilizer treatment alone. The organic fertilizer treatment increased the contribution of AOA to nitrification and decreased the contribution of AOB, thus reducing N2O and NO from nitrification. In addition, the results of the dual isotope mixing model[δ18O(N2O/H2O) vs. δ15NSP] indicated that the bacterial denitrification/nitrifying bacterial denitrification (bD/nD) process served as the primary pathway for N2O emissions in peach orchards. Partial substitution with organic fertilizers enhanced soil denitrification, resulting in larger reductions in the amounts of N2O and NO. Therefore, partial substitution of organic fertilizer is a viable measure to mitigate nitrogen oxide emissions from orchards and to achieve green and low-carbon development in agriculture.
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The effects of preterm birth, neonatal morbidities and environmental influences on infant sleep development is an important yet under-researched topic, with little known about normative sleep for infants born sick or preterm. The aim of this prospective, observational longitudinal study was to evaluate maternal perceptions and degree of bother with infant sleep behaviours and feeding outcomes across the first 9 months after discharge for sick/preterm infants cared for in the neonatal intensive care unit (NICU) and for healthy term-born infants. This paper reports outcomes for the sick/preterm cohort (I = 94) that were recruited from two NICUs in Perth, Western Australia. Total bother scores were on average 20.2% higher at 9 months than at two weeks post-discharge (p < 0.001). Increased night waking frequency, evening settling duration and crying duration were all positively associated with total bother scores. Maternal confidence scores were negatively associated with maternal bother scores; with each unit increase in confidence, maternal bother decreased by 8.5% (p < 0.001). Covariates such as birth gestation, breastfeeding status and multiple births were not associated with maternal bother. Families may benefit from additional support when experiencing increased night waking frequency and crying and settling durations in the first 9 months after discharge from NICU.
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The relation between aphids and Sclerotinia stem rot (SSR) in oilseed rape is rarely examined because they are often studied alone. We have observed a significant correlation between the number of aphids and the occurrence of SSR in our field studies. Electropenetrography (EPG) was used to evaluate the effects of Brevicoryne brassicae (Linnaeus) on two oilseed rape cultivars while acquiring, vectoring and inoculating of Sclerotinia sclerotiorum Lib. (de Bary) ascospores. The results demonstrated that aphid feeding followed by the application of an ascospore suspension significantly increased S. sclerotiorum incidence. Aphids were capable of adhering to ascospores and carrying them to healthy plants, thereby causing diseases. The results of the EPG analysis indicated that aphid feeding behaviour was significantly altered in all leaf tissue levels following infection with S. sclerotiorum. Aphids initiated their first puncture significantly sooner than the control group, began probing mesophyll cells earlier, significantly increased the frequency of both short probes and intracellular punctures and had a significantly shorter pathway duration. On infected aphid-susceptible cultivars, aphids secreted more saliva but had reduced ingestion compared with aphids feeding on non-infected oilseed rape. In addition, ascospores can affect aphid feeding behaviour by adhering to aphids. Aphids carrying ascospores punctured cells earlier, with a significant increase in the frequency and duration of short probes and cell punctures, shortened pathway durations, increased salivation and reduced ingestion compared with aphids not carrying ascospores. On aphid-susceptible cultivars, aphids carrying ascospores delayed puncture onset, but on resistant cultivars, puncture onset was shortened. There is a correlation between aphids and S. sclerotiorum. The impact of S. sclerotiorum on aphid feeding behaviour is directional, favouring the spread of the fungus. This promotion does not appear to be altered by the aphid resistance of the cultivar.
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RNA-binding proteins can regulate nucleotide metabolism and gene expression. UPF3B regulator of nonsense mediated mRNA decay (UPF3B) exhibits dysfunction in cancers. However, its role in the progression of hepatocellular carcinoma (HCC) is still insufficiently understood. Here, we found that UPF3B was markedly upregulated in HCC samples and associated with adverse prognosis in patients. UPF3B dramatically promoted HCC growth both in vivo and in vitro. Mechanistically, UPF3B was found to bind to PPP2R2C, a regulatory subunit of PP2A, boosting its mRNA degradation and activating the PI3K/AKT/mTOR pathway. E2F transcription factor 6 (E2F6) directly binds to the UPF3B promoter to facilitate its transcription. Together, the E2F6/UPF3B/PPP2R2C axis promotes HCC growth through the PI3K/AKT/mTOR pathway. Hence, it could be a promising therapeutic target for treating HCC.
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Carcinoma Hepatocelular , Regulación Neoplásica de la Expresión Génica , Neoplasias Hepáticas , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , Proteínas de Unión al ARN , Serina-Treonina Quinasas TOR , Humanos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Animales , Línea Celular Tumoral , Proteínas de Unión al ARN/metabolismo , Proteínas de Unión al ARN/genética , Serina-Treonina Quinasas TOR/metabolismo , Ratones , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteína Fosfatasa 2/metabolismo , Proteína Fosfatasa 2/genética , Transducción de Señal , Masculino , Proliferación Celular/genética , Pronóstico , Femenino , Ratones Desnudos , Regulación hacia ArribaRESUMEN
Immune thrombocytopenia (ITP) is the most common autoimmune disorder characterized by decreased platelet counts and impaired platelet production. Eltrombopag has been demonstrated to be safe and effective for children with ITP. It is reported eltrombopag can achieve a sustained response off treatment. However, data on its overall efficacy and safety profile are scarce in children. This study aimed to investigate the long-term efficacy of eltrombopag in children with ITP. Treatment overall response (OR), complete response (CR), response (R), durable response (DR), no response (NR), treatment free remission (TFR), and relapse rate, were assessed in 103 children with ITP during eltrombopag therapy. The OR rate, CR rate, R rate, DR rate, NR rate, TFR rate, and relapse rate were 67.0%, 55.3%, 11.7%, 56.3%, 33.0%, 60%, 36.2%, respectively. Importantly, we discovered that newly diagnosed ITP patients showed a higher DR rate, TFR rate and lower relapse rate compared to persistent and chronic ITP patients. Furthermore, the CR rate, DR rate, and TFR rate of 5 patients under six months were 100%. None of them suffered relapse. The most common adverse event (AEs) was hepatotoxicity (7.77%). Our study highlighted the critical role of eltrombopag as the second-line treatment in children with ITP who were intolerant to first-line therapy.
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Benzoatos , Hidrazinas , Púrpura Trombocitopénica Idiopática , Pirazoles , Humanos , Pirazoles/uso terapéutico , Pirazoles/efectos adversos , Hidrazinas/uso terapéutico , Hidrazinas/efectos adversos , Hidrazinas/administración & dosificación , Benzoatos/uso terapéutico , Benzoatos/efectos adversos , Púrpura Trombocitopénica Idiopática/tratamiento farmacológico , Púrpura Trombocitopénica Idiopática/sangre , Niño , Masculino , Femenino , Preescolar , Adolescente , Lactante , Resultado del Tratamiento , Estudios Retrospectivos , Inducción de Remisión , RecurrenciaRESUMEN
Objective: and design Mild vascular inflammation promotes the pathogenesis of hypertension. Asprosin, a newly discovered adipokine, is closely associated with metabolic diseases. We hypothesized that asprosin might led to vascular inflammation in hypertension via NLRP3 inflammasome formation. This study shows the importance of asprosin in the vascular inflammation of hypertension. Methods: Primary vascular smooth muscle cells (VSMCs) were obtained from the aorta of animals, including spontaneously hypertensive rats (SHR), Wistar-Kyoto rats (WKY), NLRP3-/- and wild-type mice. Studies were performed in VSMCs in vitro, as well as WKY and SHR in vivo. Results: Asprosin expressions were up-regulated in VSMCs and media of arteries in SHR. Asprosin overexpression promoted NLRP3 inflammasome activation via Toll-like receptor 4 (TLR4), accompanied with activation of NFκB signaling pathway in VSMCs. Exogenous asprosin protein showed similar roles in promoting NLRP3 inflammasome activation. Knockdown of asprosin restrained NLRP3 inflammasome and p65-NFκB activation in VSMCs of SHR. NLRP3 inhibitor MCC950 or NFκB inhibitor BAY11-7082 attenuated asprosin-caused VSMC proliferation and migration. Asprosin-induced interleukin-1ß production, proliferation and migration were attenuated in NLRP3-/- VSMCs. Local asprosin knockdown in common carotid artery of SHR attenuated inflammation and vascular remodeling. Conclusions: Asprosin promoted NLRP3 inflammasome activation in VSMCs by TLR4-NFκB pathway, and thereby stimulates VSMCs proliferation, migration, and vascular remodeling of SHR.
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Lassa fever (LF), caused by Lassa virus (LASV), is one of the most dangerous diseases to public health. Homologous recombination (HR) is a basic genetic power driving biological evolution. However, as a negative-stranded RNA virus, it is unknown whether HR occurs between LASVs and its influence on the outbreak of LF. In this study, after analyzing 575 S and 433 L segments of LASV collected in Africa, we found that LASV can achieve HR in both of its segments. Interestingly, although the length of S segment is less than half of the L segment, the proportion of LASVs with S recombinants is significantly higher than that with L recombinants. These results suggest that HR may be a feature of LASV, which can be set by natural selection to produce beneficial or eliminate harmful mutations for the virus, so it plays a role in LASV evolution during the outbreak of LF.
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Introduction: Dysregulation in lipid metabolism contributes to the occurrence and development of various cancers. The connection between changes in lipid metabolism and the development of intrahepatic cholangiocarcinoma remains uncertain. Our objective was to investigate the significance of blood lipid levels in patients with intrahepatic cholangiocarcinoma who have undergone surgery. Methods: Ninety-seven ICC patients who underwent surgery were retrospectively enrolled. After 92.2 months of follow-up, the Kaplan-Meier analysis and Cox proportional hazard model were used to calculate overall survival and recurrence-free survival. Results: The median age of this cohort was 56 years, and 79 (81.4 %) of them were male. Eighty-eight (90.7 %) patients presented with tumor recurrence and 73 (75.3 %) died. In multivariate analyses, high-density lipoprotein cholesterol level (<0.91 vs. ≥ 0.91 mmol/L, hazard ratio [HR] = 2.55; 95 % CI: 1.38-4.71), lymph node metastasis (Yes vs. No, HR = 2.58; 95 % CI: 1.28-5.19), etiology factor (chronic HBV infection vs. others, HR = 0.5; 95 % CI: 0.28-0.88) and multiple tumor lesions (Yes vs. No, HR = 1.85; 95 % CI: 1.01-3.39) were independent predictors of overall survival. However, only high-density lipoprotein cholesterol level (HR = 1.86; 95 % CI: 1.19-2.92) emerged as the independent factor for recurrence-free survival. High-density lipoprotein cholesterol level (HR = 2.07; 95 % CI: 1.26-3.41), etiology factor (HR = 0.49; 95 % CI: 0.29-0.84), and multiple tumor lesions (HR = 2.00; 95 % CI: 1.14-3.51) were independent predictors of early recurrence. For patients who did not experience the spread of cancer to the lymph nodes, there was a significant correlation between the level of high-density lipoprotein cholesterol and their overall survival, recurrence-free survival, and early recurrence. For patients with low pre-operation high-density lipoprotein cholesterol levels, high post-operation high-density lipoprotein cholesterol levels were associated with better prognosis. Conclusions: Low serum high-density lipoprotein cholesterol level might serve as a sign of poor clinical outcomes (overall survival and recurrence-free survival) and early recurrence among intrahepatic cholangiocarcinoma patients. Strengthening the monitoring and intervention of intrahepatic cholangiocarcinoma patients with poor prognosis might be critical for improving the prognosis.
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OBJECTIVE: To investigate the efficacy and safety of a treatment regimen based on daratumumab in patients with high-risk relapsed refractory multiple myeloma(MM) with mSMART 3.0 score. METHODS: Clinical data were collected from 16 patients with mSMART3.0 score high-risk relapsed refractory MM treated at the Affiliated Hospital of Shandong University of Traditional Chinese Medicine from May 2020 to May 2023, all of whom received daltezumab-based regimen (regimen drugs including dexamethasone, isazomib, bortezomib, lenalidomide). The efficacy and safety of the treatment were retrospectively analyzed. RESULTS: The median age of 16 patients was 63.5 (47-70) years old, including 10 cases of IgG type, 2 cases of IgA type, and 4 cases of light chain type. The curative efficacy was judged in all 16 patients, with an overall response rate of 93.75% (15/16), including 4 cases of strict complete remission (sCR), 1 case of complete remission (CR), 2 case of very good partial remission (VGPR), partial remission (PR) in 5 cases, and minor remission (MR) in 3 cases. The median follow-up time was 11(2-30) months, and the median progression-free survival and median overall survival were not achieved in 16 patients at the median follow-up period. The hematologic adverse effects of the treatment regimen using daratumumab-based were mainly neutropenia, and the non-hematologic adverse effects were mainly infusion-related adverse reactions and infections. CONCLUSION: Daratumumab-based regimen for the treatment of relapsed refractory MM patients with high risk of mSMART3.0 score has better efficacy and safety.