RESUMEN
Infection by bacterial products in the implant and endotoxin introduced by wear particles activate immune cells, enhance pro-inflammatory cytokines production, and ultimately promote osteoclast recruitment and activity. These factors are known to play an important role in osteolysis as well as potential targets for the treatment of osteolysis. Sesamin has been shown to have a variety of biological functions, such as inhibiting inflammation, anti-tumour and involvement in the regulation of fatty acid and cholesterol metabolism. However, the therapeutic effect of sesamin on osteolysis and its mechanism remain unclear. Present studies shown that in the condition of in vitro, sesamin could inhibit osteoclastogenesis and bone resorption, as well as suppressing the expression of osteoclast-specific genes. Further studies on the mechanism suggest that the effect of sesamin on human osteoclasts was mediated by blocking the ERK and NF-κB signalling pathways. Besides, sesamin was found to be effective in treating LPS-induced osteolysis by decreasing the production of pro-inflammatory cytokines and inhibiting osteoclastogenesis in vivo. Sesamin was non-toxic to heart, liver, kidney, lung and spleen. Therefore, sesamin is a promising phytochemical agent for the therapy of osteolysis-related diseases caused by inflammation and excessive osteoclast activation.
Asunto(s)
Resorción Ósea , Dioxoles , Lignanos , Osteólisis , Humanos , Animales , Ratones , Osteólisis/inducido químicamente , Osteólisis/tratamiento farmacológico , FN-kappa B/metabolismo , Osteogénesis , Lipopolisacáridos/metabolismo , Osteoclastos/metabolismo , Resorción Ósea/patología , Inflamación/patología , Citocinas/metabolismo , Ligando RANK/metabolismo , Ratones Endogámicos C57BLRESUMEN
In recent years, breast cancer (BC) has surpassed lung cancer as the most common malignant tumor worldwide and remains the leading cause of cancer death in women. The etiology of BC usually involves dysregulation of epigenetic mechanisms and aberrant expression of certain non-coding RNAs (ncRNAs). N6-methyladenosine (m6A), the most prevalent RNA modification in eukaryotes, widely exists in ncRNAs to affect its biosynthesis and function, and is an important regulator of tumor-related signaling pathways. Interestingly, ncRNAs can also regulate or target m6A modification, playing a key role in cancer progression. However, the m6A-ncRNAs regulatory network in BC has not been fully elucidated, especially the regulation of m6A modification by ncRNAs. Therefore, in this review, we comprehensively summarize the interaction mechanisms and biological significance of m6A modifications and ncRNAs in BC. Meanwhile, we also focused on the clinical application value of m6A modification in BC diagnosis and prognosis, intending to explore new biomarkers and potential therapeutic targets.
Asunto(s)
Neoplasias de la Mama , Neoplasias Pulmonares , Femenino , Humanos , Neoplasias de la Mama/genética , Adenosina/genética , Epigénesis Genética , ARN no Traducido/genéticaRESUMEN
Antibody-drug conjugates (ADCs) have demonstrated effectiveness in treating various cancers, particularly exhibiting specificity in targeting human epidermal growth factor receptor 2 (HER2)-positive breast cancer. Recent advancements in phase 3 clinical trials have broadened current understanding of ADCs, especially trastuzumab deruxtecan, in treating other HER2-expressing malignancies. This expansion of knowledge has led to the US Food and Drug Administration's approval of trastuzumab deruxtecan for HER2-positive and HER2-low breast cancer, HER2-positive gastric cancer, and HER2-mutant nonsmall cell lung cancer. Concurrent with the increasing use of ADCs in oncology, there is growing concern among health care professionals regarding the rise in the incidence of interstitial lung disease or pneumonitis (ILD/p), which is associated with anti-HER2 ADC therapy. Studies on anti-HER2 ADCs have reported varying ILD/p mortality rates. Consequently, it is crucial to establish guidelines for the diagnosis and management of ILD/p in patients receiving anti-HER2 ADC therapy. To this end, a panel of Chinese experts was convened to formulate a strategic approach for the identification and management of ILD/p in patients treated with anti-HER2 ADC therapy. This report presents the expert panel's opinions and recommendations, which are intended to guide the management of ILD/p induced by anti-HER2 ADC therapy in clinical practice.
Asunto(s)
Inmunoconjugados , Enfermedades Pulmonares Intersticiales , Receptor ErbB-2 , Humanos , Enfermedades Pulmonares Intersticiales/tratamiento farmacológico , Enfermedades Pulmonares Intersticiales/inducido químicamente , China , Inmunoconjugados/uso terapéutico , Inmunoconjugados/efectos adversos , Neumonía/tratamiento farmacológico , Femenino , Consenso , Trastuzumab/uso terapéutico , Trastuzumab/efectos adversos , Neoplasias de la Mama/tratamiento farmacológico , Camptotecina/análogos & derivadosRESUMEN
INTRODUCTION: Numerous randomized controlled trials (RCTs) have investigated PD-1/PD-L1 inhibitor-based combination therapies. The debate surrounding the potential additive clinical benefits of combination of two immune-oncology (IO) therapies for cancer patients persists. METHODS: Both published and grey sources of randomized clinical trials that compared anti-PD-1/PD-L1-based immunotherapy combinations with monotherapy in patients with advanced or metastatic solid tumors were encompassed. The primary outcome was progression-free survival (PFS), and secondary outcomes included objective response rate (ORR), overall survival (OS) and treatment-related adverse events (TRAEs). RESULTS: Our analysis encompassed 31 studies comprising 10,341 patients, which covered 12 distinct immune-oncology combination regimens. Across all patients, the immunotherapy combinations exhibited the capability to enhance the ORR (OR = 1.23 [95% CI 1.13-1.34]) and extend PFS (HR = 0.91 [95% CI 0.87-0.95]). However, the observed enhancement in OS (HR = 0.96 [95% CI 0.91-1.01]) was of no significance. Greater benefits in terms of PFS (HR = 0.82 [95% CI 0.72 to 0.93]) and OS (HR = 0.85 [95% CI 0.73 to 0.99]) may be particularly pronounced in cases where PD-L1 expression is negative. Notably, despite a heightened risk of any-grade TRAEs (OR = 1.72 [95% CI 1.40-2.11]) and grade greater than or equal to 3 TRAEs (OR = 2.01 [95% CI 1.67-2.43]), toxicity was generally manageable. CONCLUSIONS: This study suggests that incorporating an additional immunotherapy agent with PD-1/PD-L1 inhibitors can elevate the response rate and reduce the risk of disease progression, all while maintaining manageable toxicity. However, there remains a challenge in translating these primary clinical benefits into extended overall survival.
Asunto(s)
Antígeno B7-H1 , Inhibidores de Puntos de Control Inmunológico , Inmunoterapia , Neoplasias , Receptor de Muerte Celular Programada 1 , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Antígeno B7-H1/antagonistas & inhibidores , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Inmunoterapia/métodos , Inmunoterapia/efectos adversos , Neoplasias/tratamiento farmacológico , Neoplasias/inmunología , Neoplasias/terapia , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
BACKGROUND: Alzheimer's disease (AD) and frontotemporal dementia (FTD) are the two most common neurodegenerative dementias, presenting with similar clinical features that challenge accurate diagnosis. Despite extensive research, the underlying pathophysiological mechanisms remain unclear, and effective treatments are limited. This study aims to investigate the alterations in brain network connectivity associated with AD and FTD to enhance our understanding of their pathophysiology and establish a scientific foundation for their diagnosis and treatment. METHODS: We analyzed preprocessed electroencephalogram (EEG) data from the OpenNeuro public dataset, comprising 36 patients with AD, 23 patients with FTD, and 29 healthy controls (HC). Participants were in a resting state with eyes closed. We estimated the average functional connectivity using the Phase Lag Index (PLI) for lower frequencies (delta and theta) and the Amplitude Envelope Correlation with leakage correction (AEC-c) for higher frequencies (alpha, beta, and gamma). Graph theory was applied to calculate topological parameters, including mean node degree, clustering coefficient, characteristic path length, global and local efficiency. A permutation test was then utilized to assess changes in brain network connectivity in AD and FTD based on these parameters. RESULTS: Both AD and FTD patients showed increased mean PLI values in the theta frequency band, along with increases in average node degree, clustering coefficient, global efficiency, and local efficiency. Conversely, mean AEC-c values in the alpha frequency band were notably diminished, which was accompanied by decreases average node degree, clustering coefficient, global efficiency, and local efficiency. Furthermore, AD patients in the occipital region showed an increase in theta band node degree and decreased alpha band clustering coefficient and local efficiency, a pattern not observed in FTD. CONCLUSIONS: Our findings reveal distinct abnormalities in the functional network topology and connectivity in AD and FTD, which may contribute to a better understanding of the pathophysiological mechanisms of these diseases. Specifically, patients with AD demonstrated a more widespread change in functional connectivity, while those with FTD retained connectivity in the occipital lobe. These observations could provide valuable insights for developing electrophysiological markers to differentiate between the two diseases.
Asunto(s)
Enfermedad de Alzheimer , Encéfalo , Electroencefalografía , Demencia Frontotemporal , Humanos , Demencia Frontotemporal/fisiopatología , Enfermedad de Alzheimer/fisiopatología , Femenino , Masculino , Anciano , Electroencefalografía/métodos , Encéfalo/fisiopatología , Persona de Mediana Edad , Red Nerviosa/fisiopatología , Red Nerviosa/diagnóstico por imagen , Vías Nerviosas/fisiopatologíaRESUMEN
BACKGROUND: Infectious etiologies of lower respiratory tract infections (LRTIs) by the conventional microbiology tests (CMTs) can be challenging. Metagenomic next-generation sequencing (mNGS) has great potential in clinical use for its comprehensiveness in identifying pathogens, particularly those difficult-to-culture organisms. METHODS: We analyzed a total of 205 clinical samples from 201 patients with suspected LRTIs using mNGS in parallel with CMTs. mNGS results were used to guide treatment adjustments for patients who had negative CMT results. The efficacy of treatment was subsequently evaluated in these patients. RESULTS: mNGS-detected microorganisms in 91.7% (188/205) of the clinical samples, whereas CMTs demonstrated a lower detection rate, identifying microorganisms in only 37.6% (77/205) of samples. Compared to CMT results, mNGS exhibited a detection sensitivity of 93.5% and 95.4% in all 205 clinical samples and 180 bronchoalveolar lavage fluid (BALF) samples, respectively. A total of 114 patients (114/201; 56.7%) showed negative CMT results, among which 92 received treatment adjustments guided by their positive mNGS results. Notably, 67.4% (62/92) of patients demonstrated effective treatment, while 25% (23/92) experienced a stabilized condition. Subgroup analysis of cancer patients revealed that 41.9% (13/31) exhibited an effective response to treatment, and 35.5% (11/31) maintained a stable condition following medication adjustments guided by mNGS. CONCLUSION: mNGS demonstrated great potential in identifying microorganisms of clinical significance in LRTIs. The rapid turnaround time and reduced susceptibility to the impact of antimicrobial administration make mNGS a valuable supplementary tool for diagnosis and treatment decision-making for suspected LRTIs in clinical practice.
Asunto(s)
Infecciones del Sistema Respiratorio , Humanos , Infecciones del Sistema Respiratorio/diagnóstico , Infecciones del Sistema Respiratorio/tratamiento farmacológico , Secuenciación de Nucleótidos de Alto Rendimiento , Líquido del Lavado Bronquioalveolar , Metagenómica , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: Over a dozen vaccines are in or have completed phase III trials at an unprecedented speed since the World Health Organization (WHO) declared COVID-19 a pandemic. In this review, we aimed to compare and rank these vaccines indirectly in terms of efficacy and safety using a network meta-analysis. METHODS: We searched Embase, MEDLINE, and the Cochrane Library for phase III randomized controlled trials (RCTs) from their inception to September 30, 2023. Two investigators independently selected articles, extracted data, and assessed the risk of bias. Outcomes included efficacy in preventing symptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the incidence of serious adverse events (SAEs) according to vaccine type and individual vaccines in adults and elderly individuals. The risk ratio and mean differences were calculated with 95% confidence intervals using a Bayesian network meta-analysis. RESULTS: A total of 25 RCTs involving 22 vaccines were included in the study. None of vaccines had a higher incidence of SAEs than the placebo. Inactivated virus vaccines might be the safest, with a surface under the cumulative ranking curve (SUCRA) value of 0.16. BIV1-CovIran showed the highest safety index (SUCRA value: 0.13), followed by BBV152, Soberana, Gam-COVID-Vac, and ZF2001. There were no significant differences among the various types of vaccines regarding the efficacy in preventing symptomatic SARS-CoV-2 infection, although there was a trend toward higher efficacy of the mRNA vaccines (SUCRA value: 0.09). BNT162b2 showed the highest efficacy (SUCRA value: 0.02) among the individual vaccines, followed by mRNA-1273, Abdala, Gam-COVID-Vac, and NVX-CoV2373. BNT162b2 had the highest efficacy (SUCRA value: 0.08) in the elderly population, whereas CVnCoV, CoVLP + AS03, and CoronaVac were not significantly different from the placebo. CONCLUSIONS: None of the different types of vaccines were significantly superior in terms of efficacy, while mRNA vaccines were significantly inferior in safety to other types. BNT162b2 had the highest efficacy in preventing symptomatic SARS-CoV-2 infection in adults and the elderly, whereas BIV1-CovIran had the lowest incidence of SAEs in adults.
Asunto(s)
Vacunas contra la COVID-19 , COVID-19 , Ensayos Clínicos Fase III como Asunto , Metaanálisis en Red , SARS-CoV-2 , Humanos , Vacunas contra la COVID-19/efectos adversos , Vacunas contra la COVID-19/inmunología , Vacunas contra la COVID-19/administración & dosificación , COVID-19/prevención & control , COVID-19/epidemiología , SARS-CoV-2/inmunología , Ensayos Clínicos Controlados Aleatorios como Asunto , Eficacia de las Vacunas , Vacunas de Productos Inactivados/inmunología , Vacunas de Productos Inactivados/efectos adversos , Teorema de BayesRESUMEN
The two fungal species Trichophyton rubrum and Trichophyton violaceum are common pathogens on human, infecting keratinized tissue of the outer body parts. Both species are belonging to the "Trichophyton rubrum complex" and share very high similarity in the genome. Secreted proteinases, key factors for keratin degradation, are nearly identical. Contrary, the ecological niches are differing. Trichophyton rubrum preferably infects skin and nails, whereas T. violaceum preferably infects the scalp. We postulate, that differences in the protease expression contribute to differences in ecological preferences. We analyzed the expression profiles of all 22 endoprotease genes, 12 subtilisins (S8A), 5 deuterolysins (M35) and 5 fungalysins (M36), for both species. To compare the influence of the keratin source, we designed experiments with human nail keratin, sheep wool keratin and keratin free cultivation media. Samples were taken at 12 h, 24 h, 48 h and 96 h post incubation in keratin medium. The expression of the proteases is higher in wool-keratin medium compared to human nail medium, with the exception of MEP4 and SUB6. Expression in the keratin-free medium is lowest. The expression profiles of the two species are remarkable different. The expression of MEP1, MEP3, SUB5, SUB11 and SUB12 are higher in T. rubrum compared to T. violaceum. MEP2, NpIIc, NpIIe, SUB1, SUB3, SUB4, SUB7 and SUB8 are higher expressed in T. violaceum compared to T. rubrum. The differences of the protease expression in the two species may expalin the differences in the ecological niches. Further analysis are necessary to verify the hypothesis.Please check and conform the edit made in title.Here I thinke the species of strains shouldnt be capitalï¼ and the right expression should be, "Expression Profiles of Protease in Onychomycosis-Related Pathogenic Trichophyton rubrum and Tinea Capitis-Related Pathogenic Trichophyton violaceum"Author names: Please confirm if the author names are presented accurately and in the correct se-quence (given name, middle name/initial, family name). Author 1 Given name: [Jingjing] Last name [Chen], Author 2 Given name: [Yangmin] Last name [Gao], Author 3 Given name: [Shuzhen] Last name [Xiong], Author 4 Given name: [Ping] Last name [Zhan]. Also, kindly confirm the details in the metadata are correct.YesPlease check and confirm the inserted city and country are correctly identified for affiliation 3.Please change the affiliations, Affiliation 2: ²Jiangxi Provincial Clinical Research Center for Skin Diseases, Dermatology Hospital of Jiangxi Province,The Affiliated Dermatology Hospital of Nanchang University, Nanchang, 330200, Jiangxi; Affiliation 3: 3Institute of Clinical Medicine, Jiangxi Provincial People's Hospital, The First Affiliated Hospital of Nanchang Medical College,Nanchang 330001, Jiangxi. Thanks a lot!
Asunto(s)
Arthrodermataceae , Onicomicosis , Tiña del Cuero Cabelludo , Ovinos , Animales , Humanos , Péptido Hidrolasas , QueratinasRESUMEN
Candida vulturna belongs to the Candida haemulonii species complex and is phylogenetically related to C. auris. We report a C. vulturna outbreak among persons in Shanxi Province, China, during 2019-2022. Isolates were resistant to multiple antifungal drugs and exhibited enhanced adhesion and biofilm formation properties.
Asunto(s)
Candida , Candidiasis , Candidiasis/epidemiología , Candidiasis/microbiología , Antifúngicos/farmacología , Antifúngicos/uso terapéutico , China/epidemiología , Pruebas de Sensibilidad MicrobianaRESUMEN
BACKGROUND AND AIMS: Lenvatinib is a first-line drug commonly used in the treatment of advanced hepatocellular carcinoma (HCC). However, its clinical efficacy is very limited due to drug resistance. Therefore, there is a great need to explore its combination with other agents to achieve better therapeutic effects. Metformin has been demonstrated to show an anti-cancer effect. This study aimed to investigate the combined effect of lenvatinib with metformin in HCC cells both in vitro and in vivo and elucidate the possible molecular mechanisms. METHODS: Flow cytometry, colony formation, CCK-8 and transwell assays were used to study the effect of Lenvatinib-Metformin combination on the malignant behaviour of HCC cells in vitro. Constructing an animal model of tumour-bearing to study the effect of combined drugs on HCC in vivo. Western blot experiments were performed to assess the relationship between AKT and FOXO3 and the cellular translocation of FOXO3. RESULTS: Our results suggested that Lenvatinib and Metformin synergistically inhibited HCC growth and motility. Mechanistically, the combination of Lenvatinib and Metformin synergistically suppressed the activation of the AKT signalling pathway, which in turn reduced the phosphorylation level of downstream effector FOXO3 and induced its nuclear aggregation. In vivo studies further confirmed the synergistic suppression of lenvatinib with metformin in HCC growth. CONCLUSION: The Lenvatinib-Metformin combination may provide a potential therapeutic strategy to improve the prognosis of HCC patients.
Asunto(s)
Antineoplásicos , Carcinoma Hepatocelular , Neoplasias Hepáticas , Metformina , Animales , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Carcinoma Hepatocelular/patología , Línea Celular Tumoral , Neoplasias Hepáticas/patología , Metformina/farmacología , Metformina/uso terapéutico , Compuestos de Fenilurea/farmacología , Compuestos de Fenilurea/uso terapéutico , Proteínas Proto-Oncogénicas c-akt/metabolismo , HumanosRESUMEN
Although hyperhomocysteinemia (hHcys) has been recognized as an important independent risk factor in the progression of end-stage renal disease and the development of cardiovascular complications related to end-stage renal disease, the mechanisms triggering pathogenic actions of hHcys are not fully understood. The present study was mainly designed to investigate the role of HDACs in renal injury induced by hHcys. Firstly, we identified the expression patterns of HDACs and found that, among zinc-dependent HDACs, HDAC9 was preferentially upregulated in the kidney from mice with hHcys. Deficiency or pharmacological inhibition of HDAC9 ameliorated renal injury in mice with hHcys. Moreover, podocyte-specific deletion of HDAC9 significantly attenuated podocyte injury and proteinuria. In vitro, gene silencing of HDAC9 attenuated podocyte injury by inhibiting apoptosis, reducing oxidative stress and maintaining the expressions of podocyte slit diaphragm proteins. Mechanically, we proved for the first time that HDAC9 reduced the acetylation level of H3K9 in the promoter of Klotho, then inhibited gene transcription of Klotho, finally aggravating podocyte injury in hHcys. In conclusion, our results indicated that targeting of HDAC9 might be an attractive therapeutic strategy for the treatment of renal injury induced by hHcys.
Asunto(s)
Hiperhomocisteinemia , Fallo Renal Crónico , Podocitos , Animales , Ratones , Represión Epigenética , Histona Desacetilasas/genética , Histona Desacetilasas/metabolismo , Hiperhomocisteinemia/genética , Hiperhomocisteinemia/complicaciones , Hiperhomocisteinemia/metabolismo , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/genética , Fallo Renal Crónico/metabolismo , Podocitos/patologíaRESUMEN
Trichophyton rubrum and T. mentagrophytes are the most common agents of dermatomycosis, a disease affecting millions worldwide. It has been widely recognized that secreted proteases are a key factor for host colonization. Dermatophytes have an unusually high amount of secreted protease, differentially expressed, and influenced by various conditions. This study analyzed the rule and expression of secreted deuterolysin protease of the M35 protein family in these two representative dermatophyte species. All strains secreted protease and could grow on keratin as the sole carbon and nitrogen source. Adding glucose to the keratin medium reduced the growth rate. Deuterolysin genes were most strongly expressed at acid conditions. NPIIc and NPIId expression was significantly higher than the other three deuterolysins. NPIIc had a high expression level in the two T. rubrum strains but a low expression in T. mentagrophytes strains. Both T. mentagrophytes strains had a high NPIId expression at low pH. NPIIc and NPIId deletion in T. rubrum caused a minor reduction in total protease activity, indicating the redundancy of protease in dermatophytes. It was postulated that protease gene enrichment in dermatophytes allows a sophisticated regulation of protease secretion to cope with changing conditions.
Nail infections and ringworm are caused by fungi called dermatophytes. About 20% of the world's population suffers from it at least once. Dermatophytes secrete skin protein-digesting enzymes. This study demonstrates the changing enzyme profile in response to different pH levels.
Asunto(s)
Arthrodermataceae , Humanos , Animales , Arthrodermataceae/genética , Trichophyton/genética , Péptido Hidrolasas/metabolismo , Queratinas/metabolismo , Concentración de Iones de HidrógenoRESUMEN
Accumulating data demonstrate that polycyclic aromatic hydrocarbons (PAH) exposure is linked to compromised respiratory diseases. This study aimed to analyze urinary PAH metabolites and their associations with chronic obstructive pulmonary disease (COPD) in a sample size of 3015 subjects from a total population of 50,588 from the National Health and Nutrition Examination Survey (NHANES) in 2007-2016. Results showed that the most predominant metabolite was 1-Hydroxynaphthalene (1-NAP, 84%) with a geometric mean concentration of 50,265 ng/L, followed by its homologue 2-NAP (10%), both of which arose from sources including road emission, smoking and cooking. Multiple logistic regression showed that seven of the ten major PAH metabolites were correlated with increased COPD risk: including 1-NAP (OR: 1.83, 95%CI: 1.25, 2.69), 2-Hydroxyfluorene (2-FLU, OR: 2.29, 95%CI: 1.42, 3.68) and 1-Hydroxyphenanthrene (1-PHE, OR: 2.79, 95%CI: 1.85, 4.21), when compared to the lowest tertile after adjusted for covariates. Total exposure burden per PAH congener sub-group demonstrated persistent positive correlation with COPD for ∑PHE (OR: 1.80, 95%CI: 1.34, 2.43) and ∑FLU (OR: 2.74, 95%CI: 1.77, 4.23) after adjusted for covariates. To address the contribution of PAH exposure as mixture towards COPD, weighted quantile sum (WQS) regression analyses revealed that 1-NAP, 9-Hydroxyfluorene (9-FLU), 3-Hydroxyfluorene (3-FLU) and 1-PHE were among the top contributors in the associations with COPD. Our results demonstrate the contemporary yet ongoing exposure burden of PAH exposure for over a decade, particularly towards NAPs and FLUs that contribute significantly to COPD risk, calling for more timely environmental regulation.
Asunto(s)
Hidrocarburos Policíclicos Aromáticos , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Hidrocarburos Policíclicos Aromáticos/metabolismo , Encuestas Nutricionales , Estudios Longitudinales , Modelos Logísticos , Biomarcadores/orinaRESUMEN
OBJECTIVE: To evaluate the long-term outcomes of ultrasound-guided high-intensity focused ultrasound (USgHIFU) ablation of uterine fibroids classified by T2-weighted magnetic resonance imaging (T2WI-MRI). MATERIALS AND METHODS: The data of 1427 premenopausal women with symptomatic uterine fibroids who underwent USgHIFU at four teaching hospitals in China were analyzed retrospectively. The uterine fibroids were classified based on their T2WI-MRI signal intensities relative to that of skeletal muscle, myometrium and endometrium as: hypointense, isointense, heterogeneous hyperintense fibroids (HHF), slightly HHF (sHHF) and markedly HHF (mHHF), respectively. The rates of symptom relief and reintervention post-USgHIFU ablation were compared between the classified groups. RESULTS: A total of 1303 patients were followed up for 44 (40, 49) months. The symptom relief rate of the hypointense and isointense fibroids was 83.3% and 79.5%, respectively, which were significantly higher (p < .05) compared to that of HHF, sHHF and mHHF (58.3%, 44.2% and 60.4%), respectively. sHHF had the lowest symptom relief rate (p < .05). The cumulative reintervention rate for hypointense, isointense, HHF, sHHF and mHHF types were 8.8%, 10.8%, 21.4%, 39.9% and 19.8%, respectively. The reintervention rate of hypointense/isointense fibroids was significantly lower than that of HHF/mHHF/sHHF (p < .01), while sHHF had the highest re-intervention rate (p < .01). Thus, reintervention rate is inversely correlated to the rate of symptom relief. CONCLUSIONS: USgHIFU ablation is effective for hypointense, isointense, HHF and mHHF with acceptable long-term follow-up outcomes. However, sHHF is associated with a higher reintervention rate.
Asunto(s)
Ultrasonido Enfocado de Alta Intensidad de Ablación , Leiomioma , Neoplasias Uterinas , Humanos , Femenino , Neoplasias Uterinas/diagnóstico por imagen , Neoplasias Uterinas/cirugía , Estudios Retrospectivos , Imagen por Resonancia Magnética/métodos , Resultado del Tratamiento , Leiomioma/diagnóstico por imagen , Leiomioma/cirugía , Leiomioma/patología , Ultrasonido Enfocado de Alta Intensidad de Ablación/métodos , Ultrasonografía IntervencionalRESUMEN
BACKGROUND: This study aimed to explore the value of combined serum lipids with clinical symptoms to diagnose prostate cancer (PCa), and to develop and validate a Nomogram and prediction model to better select patients at risk of PCa for prostate biopsy. METHODS: Retrospective analysis of 548 patients who underwent prostate biopsies as a result of high serum prostate-specific antigen (PSA) levels or irregular digital rectal examinations (DRE) was conducted. The enrolled patients were randomly assigned to the training groups (n = 384, 70%) and validation groups (n = 164, 30%). To identify independent variables for PCa, serum lipids (TC, TG, HDL, LDL, apoA-1, and apoB) were taken into account in the multivariable logistic regression analyses of the training group, and established predictive models. After that, we evaluated prediction models with clinical markers using decision curves and the area under the curve (AUC). Based on training group data, a Nomogram was developed to predict PCa. RESULTS: 210 (54.70%) of the patients in the training group were diagnosed with PCa. Multivariate regression analysis showed that total PSA, f/tPSA, PSA density (PSAD), TG, LDL, DRE, and TRUS were independent risk predictors of PCa. A prediction model utilizing a Nomogram was constructed with a cut-off value of 0.502. The training and validation groups achieved area under the curve (AUC) values of 0.846 and 0.814 respectively. According to the decision curve analysis (DCA), the prediction model yielded optimal overall net benefits in both the training and validation groups, which is better than the optimal net benefit of PSA alone. After comparing our developed prediction model with two domestic models and PCPT-RC, we found that our prediction model exhibited significantly superior predictive performance. Furthermore, in comparison with clinical indicators, our Nomogram's ability to predict prostate cancer showed good estimation, suggesting its potential as a reliable tool for prognostication. CONCLUSIONS: The prediction model and Nomogram, which utilize both blood lipid levels and clinical signs, demonstrated improved accuracy in predicting the risk of prostate cancer, and consequently can guide the selection of appropriate diagnostic strategies for each patient in a more personalized manner.
Asunto(s)
Nomogramas , Neoplasias de la Próstata , Masculino , Humanos , Antígeno Prostático Específico , Estudios Retrospectivos , Neoplasias de la Próstata/patología , Biopsia , Factores de RiesgoRESUMEN
Increasing evidence have demonstrated that early-life exposure to environmental toxicants elevates risk of allergic asthma. Cadmium (Cd) is widely present in the environment. The purposes of this study were to evaluate the impact of early-life Cd exposure on susceptibility to ovalbumin (OVA)-evoked allergic asthma. Newly weaned mice were subjected to a low concentration of CdCl2 (1 mg/L) by drinking water for 5 consecutive weeks. Penh value, an index of airway obstruction, was increased in OVA-stimulated and challenged pups. Abundant inflammatory cells were observed in the lung of OVA-exposed pups. Goblet cell hyperplasia and mucus secretion were shown in the airway of OVA-stimulated and challenged pups. Early-life Cd exposure exacerbated OVA-evoked airway hyperreactivity, Goblet cell hyperplasia and mucus secretion. The in vitro experiments showed that mucoprotein gene MUC5AC mRNA was upregulated in Cd-exposed bronchial epithelial cells. Mechanistically, endoplasmic reticulum (ER) stress-related molecules GRP78, p-eIF2α, CHOP, p-IRE1α and spliced XBP-1 (sXBP-1) were elevated in Cd-subjected bronchial epithelial cells. The blockade of ER stress, using chemical inhibitor 4-PBA or sXBP-1 siRNA interference, attenuated Cd-induced MUC5AC upregulation in bronchial epithelial cells. These results indicate that early-life Cd exposure aggravates OVA-induced allergic asthma partially through inducing ER stress in bronchial epithelial cells.
Asunto(s)
Asma , Cadmio , Ratones , Animales , Ovalbúmina , Cadmio/toxicidad , Endorribonucleasas , Hiperplasia/patología , Proteínas Serina-Treonina Quinasas , Asma/inducido químicamente , Asma/patología , Pulmón/patología , Ratones Endogámicos BALB CRESUMEN
OBJECTIVE: To evaluate the feasibility and effectiveness of single ultrasound-guided high-intensity focused ultrasound (USgHIFU) ablation in managing placenta accreta spectrum (PAS) disorder. MATERIALS AND METHODS: We retrospectively analyzed 40 PAS patients between April 2017 and October 2021. All the patients received one session of HIFU treatment. Regular follow-up was done after HIFU treatment until normal menstruation returned and placental tissue disappeared. The patient's reproductive-related outcomes were obtained through telephone interviews. RESULTS: The median follow-up time for the 40 patients was 30.50 (15.75-44.00) months and the mean placental tissue elimination time was 45.29 ± 33.32 days. The mean duration of bloody lochia was 13.43 ± 10.01 days, with no incidences of severe bleeding. Notably, Linear regression analysis showed that the residual placenta volume before HIFU was a factor affecting the duration of bloody lochia after HIFU (R2 = 0.284, B = 0.062, P = 0.000). The normal menstrual return time was 58.71 ± 31.14 days. One (2.50%) patient developed an infection. Two (5.00%) patients were subjected to ultrasound-guided suction curettage for persistent vaginal discharge for more than one month without infection. Notably, 7 of the 18 patients who expressed reproductive plans became pregnant during the 4 to 53 months of follow-up without placental abnormalities. The remaining 11 patients were on contraceptives. CONCLUSIONS: Single HIFU is an effective treatment option for managing PAS. However, future studies on further treatment strategies to reduce complications and promote patient recovery after HIFU ablation are desirable.
Asunto(s)
Ultrasonido Enfocado de Alta Intensidad de Ablación , Placenta Accreta , Embarazo , Humanos , Femenino , Placenta Accreta/diagnóstico por imagen , Placenta Accreta/cirugía , Placenta , Estudios Retrospectivos , Resultado del Tratamiento , Ultrasonografía IntervencionalRESUMEN
Tinea capitis (TC) in adults is much less frequently diagnosed in comparison to TC in children. In this study, we explored retrospectively adult TC in a specialized dermatology hospital, located in South China, during the years 2007-2021. Among 1037 TC cases, 168 (16.2%) patients were older than 18 years. The majority of adults with TC, 77.38% (130/168), were older than 40, with a peak in the age of 51-60 years (40/168, 23.81%). Before presenting at our hospital, many of patients did not got proper treatment due to misdiagnosis or simply did not consulted an appropriate clinic. 60.71% (102/168) of the patients reported symptoms lasting for more than 1 year and 29.76% (50/168) reported chronic scalp problems of at least 10 years. And 27.38% (46/168) of the patients had an immunocompromised status, including long-term use of corticosteroids shampoo, type 2 diabetes mellitus (DM), psoriasis vulgaris, rheumatoid arthritis, systemic lupus erythematosus or bullous pemphigoid. As for clinical presentation, 87.5% (147/168) of the cases presented as black dot type of TC and anthropophilic dermatophytes were the predominant etiology, with Trichophyton violaceum (126), T. tonsurans (15), T. rubrum (8) and T. shoenleinii (6). Grey patch type of TC (3.57%, 6/168) was seldom in Jiangxi Province and zoophilic/geophilic dermatophytes were rare. Our study indicates that anthropophilic Trichophyton species can cause long-lasting TC in adults. Not in all cases, the manifestation had symptom clearly indicating a dermatophyte-related TC. Thus, patients with long-lasting scalp inflammation, also older ones, should be examined for the presence of dermatophyte-related TC.
Asunto(s)
Diabetes Mellitus Tipo 2 , Tiña del Cuero Cabelludo , Niño , Humanos , Adulto , Persona de Mediana Edad , Estudios Retrospectivos , Tiña del Cuero Cabelludo/epidemiología , Tiña del Cuero Cabelludo/tratamiento farmacológico , Trichophyton , Cuero Cabelludo , MicrosporumRESUMEN
Objective: To investigate the diagnostic value of serum pepsinogen (PG) â /PGâ ¡ combined with tumor markers for Helicobacter pylori ( Hp)-positive early-stage gastric cancer. Methods: A retrospective study was conducted with the clinical data of 109 patients with gastric cancer (the gastric cancer group), 115 patients with chronic atrophic gastritis (the benign group), 112 cases of low-grade intraepithelial neoplasia (the low grade group), 109 cases of high-grade intraepithelial neoplasia (the high grade group), and 104 healthy subjects who underwent the relevant screening tests as part of their general physical examination (the healthy group). All the subjects were admitted to or received care at our hospital between May 2018 and April 2021. The levels of serum PGâ , PGâ ¡, carcinoembryonic antigen (CEA), carbohydrate antigen 199 (CA199), and carbohydrate antigen 724 (CA724), and Hp infection status were examined. The findings for these indicators were compared among the groups, and the differences in serum indicators in Hp-positive and Hp-negative patients were compared. The diagnostic value of serum PGâ /PGâ ¡ combined with tumor markers for Hp-positive early-stage gastric cancer was assessed with receiver operating characteristic (ROC) curve. Results: The serum levels of PGâ and PGâ /PGâ ¡ decreased in successive order in the healthy group, the benign group, the low grade group, the high grade group, and the gastric cancer group ( P<0.05). The serum levels of PGâ ¡, CEA, CA199, and CA724 in the gastric cancer group, the high grade group, and the low grade group were all higher than those in the healthy group and the benign group ( P<0.05). The Hp-positive rates of the gastric cancer group, the high grade group, the low grade group and the benign group were higher than that of the healthy group ( P<0.01). The levels of serum PGâ , PGâ ¡, CEA, CA199, and CA724 of the Hp-positive subjects of the healthy group, the benign group, the low grade group, the high grade group, and the gastric cancer group were higher than those of the Hp-negative subjects ( P<0.05), while their PGâ /PGâ ¡ levels were always lower than those of the Hp-negative persons ( P<0.05). The specificity and area under the curve ( AUC) of serum PGâ /PGâ ¡, CEA, CA199, and CA724 in the combined diagnosis of Hp-positive early-stage gastric cancer were higher than those of each indicator used alone in diagnosis ( P<0.05). In the gastric cancer group, the proportion of patients with PGâ /PGâ ¡>2.32 was lower in the Hp-positive patients than that in the Hp-negative patients ( P<0.05), while the proportions of patients with CEA>66.99 ng/mL, CA199>110.35 U/mL, and CA724>44.20 U/mL were higher in the Hp-positive patients than those in the Hp-negative patients ( P<0.05). Conclusion: Testing PGâ /PGâ ¡ in combination with CEA, CA199, and CA724 results in better diagnostic value for Hp-positive early-stage gastric cancer.
Asunto(s)
Infecciones por Helicobacter , Helicobacter pylori , Neoplasias Gástricas , Humanos , Biomarcadores de Tumor , Pepsinógeno C , Antígeno Carcinoembrionario , Pepsinógeno A , Neoplasias Gástricas/complicaciones , Neoplasias Gástricas/diagnóstico , Estudios Retrospectivos , Carbohidratos , Infecciones por Helicobacter/complicaciones , Infecciones por Helicobacter/diagnósticoRESUMEN
The stimulator of interferon genes (STING) pathway is important for anticancer immune responses. However, the relative contributions of host and tumour STING in anti-programmed cell death protein 1 (anti-PD-1) inhibitor responses in non-small cell lung cancer (NSCLC) are unknown. STING expression in tumour and blood was associated with anti-PD-1 therapy in NSCLC patients; Moreover, loss of PD-1 inhibitor therapeutic potency was demonstrated in STING KO (knock out) splenocytes and STING KO mice. STING knock-down in tumour cells had no effect. STING on CD8+ T cells and host cells, not tumour cells, correlated with clinical effect of anti-PD-1 therapy in NSCLC patients. Finally, adoptive transfer of CD8+ T cells restored PD-1 inhibitor anticancer effects. STING in host cells but not in tumour cells mediates anti-PD-1 inhibitor responses in cancer immunotherapy and could be used to select advantageous NSCLC patients from immunotherapy.