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1.
Chin Med J (Engl) ; 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38557731

RESUMO

BACKGROUND: Sentinel lymph node (SLN) biopsy is gradually accepted as the standard of care in breast cancer patients with down-staged axillary disease after neoadjuvant chemotherapy (NAC). However, it is still difficult to precisely define pre-NAC clinical node-positive (cN1) and post-NAC clinical node-negative (ycN0). This prospective single-center trial was designed to evaluate the feasibility and accuracy of standard targeted axillary dissection (TAD) after NAC in highly selective pre-NAC cN1 patients (not considering ultrasound-based axillary ycN staging). METHODS: This prospective trial included patients with initial pre-NAC cT1-3N1M0 invasive breast cancer but with a rigorous definition of cN1 from the Affiliated Cancer Hospital of Zhengzhou University. When NAC was effective (including complete and partial responses) and preoperative axillary palpation was negative, preoperative ultrasound-based axillary staging was not considered, and all patients underwent TAD followed by axillary lymph node (LN) dissection. The detection rate (DR) and false-negative rate (FNR) of TAD were calculated. RESULTS: A total of 82 patients were included, and 77 of them were eligible for data analysis. The DR for TAD was 94.8% (73/77). There were 26 patients with one abnormal LN at the time of diagnosis based on ultrasound, 45 patients with two, and 2 patients with three. One patient had one TAD LN, four patients had two TAD LNs, and 68 patients had three or more TAD LNs. Preoperative axillary palpation yielded negative results for all 73 patients who successfully underwent TAD. Preoperative ultrasound-based ycN0 and ycN+ conditions were detected for 52 and 21 cases, respectively. The FNR was 7.4% (2/27) for standard TAD (≥3 SLNs), which was lower than that of all successful TAD (≥1 SLN; 10.0%, 3/30). CONCLUSIONS: In rigorously defined pre-NAC cN1 breast cancer patients, standard TAD is feasible for those with negative axillary palpation after NAC, and FNR is also less than 10%. REGISTRATION: chictr.org.cn, ChiCTR2100049093.

2.
Front Microbiol ; 15: 1337185, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38596381

RESUMO

Introduction: Alcoholic-associated liver diseases (ALD) are now widespread issues worldwide. Alcoholic-induced chronic dysbiosis of the gut microbiota is one of the factors in the pathophysiology of ALD. Methods: In this work, we employed a chronic-binge ethanol feeding mice model, as described in a previous report. Results: Our findings demonstrate that hepatic inflammatory injury damage and accumulation of fat can be effectively reduced in mice with ALD by altering the gut microbiota utilizing Bacillus coagulans. Treatment with B. coagulans significantly modulates the levels of TNF-α, IL-1ß, and IL-22 cytokines while maintaining tight junction proteins and mucin protein expressions to support intestinal barrier function restoration. Treatment with B. coagulans also alters the composition of the gut microbiota and increases the production of short-chain fatty acids (SCFAs). Discussion: This is mostly due to B. coagulans promotes the growth of bacteria that produce SCFAs, such as Ruminococcus species and Akkermansia, while inhibiting the growth of pathogenic bacteria like Escherichia Shigella. Moreover, treatment with B. coagulans causes levels of 2-Ketobutyric acid, ketoleucine, and indoleacetic acid increase while homovanillic acid and 3'-O-Methylguanosine metabolites decrease significantly. This study facilitates the development of therapeutic and preventive strategies for ALD using lactic acid bacteria.

3.
Vet Res ; 55(1): 52, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38622656

RESUMO

Clostridium perfringens (C. perfringens) infection is recognized as one of the most challenging issues threatening food safety and perplexing agricultural development. To date, the molecular mechanisms of the interactions between C. perfringens and the host remain poorly understood. Here, we show that stimulator of interferon genes (STING)-dependent trained immunity protected against C. perfringens infection through mTOR signaling. Heat-killed Candida albicans (HKCA) training elicited elevated TNF-α and IL-6 production after LPS restimulation in mouse peritoneal macrophages (PM). Although HKCA-trained PM produced decreased levels of TNF-α and IL-6, the importance of trained immunity was demonstrated by the fact that HKCA training resulted in enhanced bacterial phagocytic ability and clearance in vivo and in vitro during C. perfringens infection. Interestingly, HKCA training resulted in the activation of STING signaling. We further demonstrate that STING agonist DMXAA is a strong inducer of trained immunity and conferred host resistance to C. perfringens infection in PM. Importantly, corresponding to higher bacterial burden, reduction in cytokine secretion, phagocytosis, and bacterial killing were shown in the absence of STING after HKCA training. Meanwhile, the high expression levels of AKT/mTOR/HIF1α were indeed accompanied by an activated STING signaling under HKCA or DMXAA training. Moreover, inhibiting mTOR signaling with rapamycin dampened the trained response to LPS and C. perfringens challenge in wild-type (WT) PM after HKCA training. Furthermore, STING­deficient PM presented decreased levels of mTOR signaling-related proteins. Altogether, these results support STING involvement in trained immunity which protects against C. perfringens infection via mTOR signaling.


Assuntos
Infecções por Clostridium , Animais , Camundongos , Infecções por Clostridium/veterinária , Clostridium perfringens , Interleucina-6 , Lipopolissacarídeos , Serina-Treonina Quinases TOR , Imunidade Treinada , Fator de Necrose Tumoral alfa/metabolismo
4.
Cell Commun Signal ; 22(1): 227, 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38610001

RESUMO

BACKGROUND: Laryngeal squamous cell carcinoma (LSCC) is one of the most common malignant tumors of the head and neck. Vasculogenic mimicry (VM) is crucial for tumor growth and metastasis and refers to the formation of fluid channels by invasive tumor cells rather than endothelial cells. However, the regulatory mechanisms underlying VM during the malignant progression of LSCC remain largely unknown. METHODS: Gene expression and clinical data for LSCC were obtained from the TCGA and Gene GEO (GSE27020) databases. A risk prediction model associated with VM was established using LASSO and Cox regression analyses. Based on their risk scores, patients with LSCC were categorized into high- and low-risk groups. The disparities in immune infiltration, tumor mutational burden (TMB), and functional enrichment between these two groups were examined. The core genes in LSCC were identified using the machine learning (SVM-RFE) and WGCNA algorithms. Subsequently, the involvement of bone morphogenetic protein 2 (BMP2) in VM and metastasis was investigated both in vitro and in vivo. To elucidate the downstream signaling pathways regulated by BMP2, western blotting was performed. Additionally, ChIP experiments were employed to identify the key transcription factors responsible for modulating the expression of BMP2. RESULTS: We established a new precise prognostic model for LSCC related to VM based on three genes: BMP2, EPO, and AGPS. The ROC curves from both TCGA and GSE27020 validation cohorts demonstrated precision survival prediction capabilities, with the nomogram showing some net clinical benefit. Multiple algorithm analyses indicated BMP2 as a potential core gene. Further experiments suggested that BMP2 promotes VM and metastasis in LSCC. The malignant progression of LSCC is promoted by BMP2 via the activation of the PI3K-AKT signaling pathway, with the high expression of BMP2 in LSCC resulting from its transcriptional activation by runt-related transcription factor 1 (RUNX1). CONCLUSION: BMP2 predicts poor prognosis in LSCC, promotes LSCC VM and metastasis through the PI3K-AKT signaling pathway, and is transcriptionally regulated by RUNX1. BMP2 may be a novel, precise, diagnostic, and therapeutic biomarker of LSCC.


Assuntos
Proteína Morfogenética Óssea 2 , Neoplasias de Cabeça e Pescoço , Humanos , Subunidade alfa 2 de Fator de Ligação ao Core , Células Endoteliais , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Transdução de Sinais
5.
Exp Cell Res ; : 114052, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38636651

RESUMO

Trained immunity is mechanistically defined as the metabolically and epigenetically mediated long-term functional adaptation of the innate immune system, characterized by a heightened response to a secondary stimulation. Given appropriate activation, trained immunity represents an attractive anti-infective therapeutic target. Nevertheless, excessive immune response and subsequent inflammatory cascades may contribute to pathological tissue damage, indicating that the negative impacts of trained immunity appear to be significant. In this study, we show that innate immune responses such as the production of extracellular traps, pro-inflammatory cytokines, and autophagy-related proteins were markedly augmented in trained BMDMs. Furthermore, heat-killed C. albicans priming promotes the activation of the AIM2 inflammasome, and AIM2-/- mice exhibit impaired memory response induced by heat-killed C. albicans. Therefore, we establish that the AIM2 inflammasome is involved in trained immunity and emerges as a promising therapeutic target for potentially deleterious effects. Dihydroartemisinin can inhibit the memory response induced by heat-killed C. albicans through modulation of mTOR signaling and the AIM2 inflammasome. The findings suggest that dihydroartemisinin can reduce the induction of trained immunity by heat-killed C. albicans in C57BL/6 mice. Dihydroartemisinin is one such therapeutic intervention that has the potential to treat of diseases characterized by excessive trained immunity.

6.
ESC Heart Fail ; 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38641904

RESUMO

AIMS: The utility of growth differentiation factor-15 (GDF-15) in predicting long-term adverse outcomes in heart failure (HF) patients is not well established. This study explored the relationship between GDF-15 levels and adverse outcomes in HF patients across various ejection fraction (EF) phenotypes associated with coronary heart disease (CHD) and evaluated the added prognostic value of incorporating GDF-15 into the Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) risk score-based model. METHODS AND RESULTS: This single-centre cohort study included 823 HF patients, categorized into 230 (27.9%) reduced EF (HFrEF), 271 (32.9%) mid-range EF (HFmrEF), and 322 (39.1%) preserved EF (HFpEF) groups. The median age was 68.0 years (range: 56.0-77.0), and 245 (29.8%) were females. Compared with the HFrEF and HFmrEF groups, the HFpEF group had a higher GDF-15 concentration (P = 0.002) and a higher MAGGIC risk score (P < 0.001). We examined the associations between GDF-15 levels and the risks of all-cause mortality and HF rehospitalization using Cox regression models. The C-index, integrated discrimination improvement (IDI), and net reclassification improvement (NRI) metrics were employed to assess the incremental prognostic value. During the 9.4 year follow-up period, 425 patients died, and 484 were rehospitalized due to HF. Multivariate Cox regression analysis revealed that elevated GDF-15 levels were significantly associated with an increased risk of all-cause mortality [hazard ratio (HR) = 1.36, 95% confidence interval (CI): 1.20-1.54; P < 0.001] and HF rehospitalization (HR = 1.75, 95% CI: 1.57-1.95; P < 0.001) across all HF phenotypes. This association remained significant when GDF-15 was treated as a categorical variable (high GDF-15 group: all-cause death: HR = 1.73, 95% CI: 1.40-2.14; P < 0.001; HF rehospitalization: HR = 3.37, 95% CI: 2.73-4.15; P < 0.001). Inclusion of GDF-15 in the MAGGIC risk score-based model provided additional prognostic value for all HF patients (Δ C-index = 0.021, 95% CI: 0.002-0.041; IDI = 0.011, 95% CI: 0.001-0.025; continuous NRI = 0.489, 95% CI: 0.174-0.629) and HF rehospitalization (Δ C-index = 0.034, 95% CI: 0.005-0.063; IDI = 0.021, 95% CI: 0.007-0.032; continuous NRI = 0.307, 95% CI: 0.147-0.548), particularly in the HFpEF subgroup. CONCLUSIONS: GDF-15 is identified as an independent risk factor for adverse outcomes in HF patients across the entire EF spectrum in the context of CHD. Integrating GDF-15 into the MAGGIC risk score-based model enhances its prognostic capability for adverse outcomes in the general HF population. This incremental prognostic effect was observed specifically in the HFpEF subgroup and not in other subgroups.

7.
Artigo em Inglês | MEDLINE | ID: mdl-38602465

RESUMO

With the widespread use of antibiotics, the incidence of antibiotic resistance in microorganisms has increased. Monochamus alternatus is a trunk borer of pine trees. This study aimed to investigate the in vitro antimicrobial and biological characteristics of Enterococcus casseliflavus TN-47 (PP411196), isolated from the gastrointestinal tract of M. alternatus in Jilin Province, PR China. Among 13 isolates obtained from the insects, five were preliminarily screened for antimicrobial activity. E. casseliflavus TN-47, which exhibited the strongest antimicrobial activity, was identified. E. casseliflavus TN-47 possessed antimicrobial activity against Staphylococcus aureus USA300 and Salmonella enterica serovar Pullorum ATCC 19945. Furthermore, E. casseliflavus TN-47 was sensitive to tetracyclines, penicillins (ampicillin, carbenicillin, and piperacillin), quinolones and nitrofuran antibiotics, and resistant to certain beta-lactam antibiotics (oxacillin, cefradine and cephalexin), macrolide antibiotics, sulfonamides and aminoglycosides. E. casseliflavus TN-47 could tolerate low pH and pepsin-rich conditions in the stomach and grow in the presence of bile acids. E. casseliflavus TN-47 retained its strong auto-aggregating ability and hydrophobicity. This strain did not exhibit any haemolytic activity. These results indicate that E. casseliflavus TN-47 has potential as a probiotic. This study provides a theoretical foundation for the future applications of E. casseliflavus TN-47 and its secondary metabolites in animal nutrition and feed.


Assuntos
Besouros , Enterococcus , Ácidos Graxos , Animais , Filogenia , Análise de Sequência de DNA , RNA Ribossômico 16S/genética , DNA Bacteriano/genética , Técnicas de Tipagem Bacteriana , Composição de Bases , Ácidos Graxos/química , Antibacterianos/farmacologia , Oxacilina
8.
Exp Eye Res ; : 109906, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38657786

RESUMO

Pediatric cataract, including congenital and developmental cataract, is a kind of pediatric vision-threatening disease with extensive phenotypic heterogeneity and multiple mechanisms. We aimed to investigate the metabolite profile of aqueous humor (AH) in patients with pediatric cataracts, and identify underlying mutual correlations between differential metabolites. Metabolomic profiles of AH were analyzed and compared between pediatric cataract patients (n=33) and age-related cataract patients without metabolic diseases (n=29), using global untargeted metabolomics with ultra-high-performance liquid chromatography tandem mass spectrometry. Principal component analysis, partial least squares discriminant analysis and heat map were applied. Enriched pathway analysis was conducted using Kyoto Encyclopedia of Genes and Genomes. Receiver-operating characteristic (ROC) analyses were employed to select potential biomarkers. A total of 318 metabolites were identified, of which 54 differential metabolites (25 upregulated and 29 downregulated) were detected in pediatric cataract group compared with controls (variable importance of projection > 1.0, fold change ≥ 1.5 or ≤ 0.667 and P < 0.05). A significant accumulation of N-Acetyl-Dl-glutamic acid was observed in pediatric cataract group. The differential metabolites were mainly enriched in histidine metabolism (increased L-Histidine and decreased 1-Methylhistamine) and the tryptophan metabolism (increased N-Formylkynurenine and L-Kynurenine). 5-Aminosalicylic acid showed strong positive mutual inter-correlation with L-Tyrosinemethylester and N,N-Diethylethanolamine, both of which were down-regulated in pediatric cataract group. The ROC analysis implied 11 metabolites served as potential biomarkers for pediatric cataract patients (all area under the ROC curve ≥ 0.900). These results illustrated novel potential metabolites and metabolic pathways in pediatric cataract, which provides new insights into the pathophysiology of pediatric cataract.

9.
Br J Psychol ; 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38635309

RESUMO

Greedy phenomena have dramatically increased in societies. However, despite the universality of greedy behaviour, empirical research on the causes of greed is scarce. In this context, we propose that perceived economic inequality may be an important factor influencing greed. Study 1 provided primary evidence of a positive relationship between perceived economic inequality and greed, based on data from a large-scale social survey (CFPS 2018, N = 14,317). Employing well-established questionnaires, Study 2A (N = 200) and Study 2B (N = 399) revealed that perceived economic inequality positively predicts greed, with relative deprivation playing a mediating role. Study 3A (N = 200) and Study 3B (N = 200) manipulated perceived economic inequality to provide causal evidence of its effects on greed and to replicate the mediating effect of relative deprivation. Finally, Study 4 (N = 372), using a blockage manipulation design, showed that the effect of perceived economic inequality on greed significantly decreases when relative deprivation is suppressed. In summary, the results of these six studies consistently suggest that perceived economic inequality positively affects greed and that this effect is mediated by relative deprivation.

10.
FASEB J ; 38(8): e23631, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38661062

RESUMO

Recurrent miscarriage (RM) is related to the dysfunction of extravillous trophoblast cells (EVTs), but the comprehensive mechanisms remain largely unexplored. We analyzed single-cell RNA sequencing (scRNA-seq), bulk RNA sequencing and microarray datasets obtained from Gene Expression Omnibus (GEO) database to explore the hub genes in the mechanisms of RM. We identified 1724 differentially expressed genes (DEGs) in EVTs from the RM, and they were all expressed along the trajectory of EVTs. These DEGs were associated with hypoxia and glucose metabolism. Single-cell Regulatory Network Inference and Clustering (SCENIC) analysis revealed that E2F transcription factor (E2F) 8 (E2F8) was a key transcription factor for these DEGs. And the expression of ENO1 can be positively regulated by E2F8 via RNA sequencing analysis. Subsequently, we performed immunofluorescence assay (IF), plasmid transfection, western blotting, chromatin immunoprecipitation (ChIP), real-time quantitative polymerase chain reaction (qRT-PCR), and transwell assays for validation experiments. We found that the expression of alpha-Enolase 1 (ENO1) was lower in the placentas of RM. Importantly, E2F8 can transcriptionally regulate the expression of ENO1 to promote the invasion of trophoblast cells by inhibiting secreted frizzled-related protein 1/4 (SFRP1/4) to activate Wnt signaling pathway. Our results suggest that ENO1 can promote trophoblast invasion via an E2F8-dependent manner, highlighting a potential novel target for the physiological mechanisms of RM.


Assuntos
Aborto Habitual , Biomarcadores Tumorais , Proteínas de Ligação a DNA , Fosfopiruvato Hidratase , Trofoblastos , Proteínas Supressoras de Tumor , Humanos , Trofoblastos/metabolismo , Feminino , Fosfopiruvato Hidratase/metabolismo , Fosfopiruvato Hidratase/genética , Gravidez , Proteínas Supressoras de Tumor/metabolismo , Proteínas Supressoras de Tumor/genética , Aborto Habitual/metabolismo , Aborto Habitual/genética , Aborto Habitual/patologia , Proteínas de Ligação a DNA/metabolismo , Proteínas de Ligação a DNA/genética , Adulto , Movimento Celular
11.
Transl Vis Sci Technol ; 13(3): 15, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38502141

RESUMO

Purpose: To derive an effective nomogram for predicting Marfan syndrome (MFS) in children with congenital ectopia lentis (CEL) using regularly collected data. Methods: Diagnostic standards (Ghent nosology) and genetic test were applied in all patients with CEL to determine the presence or absence of MFS. Three potential MFS predictors were tested and chosen to build a prediction model using logistic regression. The predictive performance of the nomogram was validated internally through time-dependent receiver operating characteristic curves, calibration curves, and decision curve analysis. Results: Eyes from 103 patients under 20 years old and with CEL were enrolled in this study. Z score of body mass index (odds ratio [OR] = 0.659; 95% confidence interval [CI], 0.453-0.958), corneal curvature radius (OR = 3.397; 95% CI, 1.829-6.307), and aortic root diameter (OR = 2.342; 95% CI, 1.403-3.911) were identified as predictors of MFS. The combination of the above predictors shows good predictive ability, as indicated by area under the curve of 0.889 (95% CI, 0.826-0.953). The calibration curves showed good agreement between the prediction of the nomogram and the actual observations. In addition, decision curve analysis showed that the nomogram was clinically useful and had better discriminatory power in identifying patients with MFS. For better individual prediction, an online MFS calculator was created. Conclusions: The nomogram provides accurate and individualized prediction of MFS in children with CEL who cannot be identified with the Ghent criteria, enabling clinicians to personalize treatment plans and improve MFS outcomes. Translational Relevance: The prediction model may help clinicians identify MFS in its early stages, which could reduce the likelihood of developing severe symptoms and improve MFS outcomes.


Assuntos
Ectopia do Cristalino , Síndrome de Marfan , Criança , Humanos , Adulto Jovem , Adulto , Ectopia do Cristalino/diagnóstico , Síndrome de Marfan/complicações , Síndrome de Marfan/diagnóstico , Nomogramas , Olho
12.
Oncologist ; 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38537665

RESUMO

BACKGROUND: According to the American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) criteria, both immunohistochemical HER2 (3+) and HER2 (2+)/in situ hybridization (ISH) amplified [HER2 (2+)/ISH+] breast cancers (BCs) fall under the HER2-positive BC category. However, there is a lack of studies exploring the difference of neoadjuvant therapeutic response between patients with HER2 (3+) and HER2 (2+)/ISH+ early BC. We aimed to evaluate the neoadjuvant therapeutic response, long-term outcome, and intrinsic subtype heterogeneity between HER2 (3+) and HER2 (2+)/ISH+ BC. METHODS: We examined 2 distinct cohorts. Cohort 1 (C1) encompassed 2648 patients with HER2-positive early BC diagnoses, and they received neoadjuvant therapy (NT) and surgery between January 1, 2009 and December 31, 2022, from the Shanghai Jiao Tong University Breast Cancer Data Base. Cohort 2 (C2) comprised 135 patients with early-stage HER2-positive BC who underwent NT and surgery at Henan Cancer Hospital from January 1, 2021, to December 31, 2022. These patients had available genomic and transcriptomic data at their disposal. C1 and C2 were further categorized into 2 patient cohorts as follows: (1) patients with IHC HER2 (3+) early BC [HER2 (3+) group], (2) patients with HER2 (2+)/ISH+ early BC [HER2 (2+)/ISH+ group]. Among those excluded from the analysis were patients < 18 years or >80 years of age. Clinicopathological parameters, long-term outcomes, and intrinsic subtypes were analyzed. RESULTS: In the C1 population, 83.7% had HER2 (3+) BC, while 16.3% had HER2 (2+)/ISH+ BC. Patients with HER2 (3+) had a significantly higher pathological complete response (PCR) rate (38.9%) than patients with HER2 (2+)/ISH+ (18.1%; P < .001), but the disease-free survival (DFS) was comparable after a median follow-up of 29 months (P = .556). The addition of trastuzumab or trastuzumab plus pertuzumab to neoadjuvant chemotherapy (NAC) improved PCR rates and DFS in HER2 (3+) BC but not in HER2 (2+)/ISH+ BC. In the C2 population, 97.75% HER2 (3+) and 52.17% HER2 (2+)/ISH+ were HER2 enriched (HER2E) subtype (P < .001). HER2E showed increased PCR rates compared to non-HER2E (P = .004). CONCLUSIONS: Compared to HER2 (3+) BC, the limited effectiveness of neoadjuvant trastuzumab and pertuzumab therapy for HER2 (2+)/ISH+ BC is due to subtype heterogeneity. Reassessment of targeted therapy efficacy in patients with HER2 (2+)/ISH+ BC is essential.

13.
Chin J Cancer Res ; 36(1): 55-65, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38455369

RESUMO

Objective: Despite cardiotoxicity overlap, the trastuzumab/pertuzumab and anthracycline combination remains crucial due to significant benefits. Pegylated liposomal doxorubicin (PLD), a less cardiotoxic anthracycline, was evaluated for efficacy and cardiac safety when combined with cyclophosphamide and followed by taxanes with trastuzumab/pertuzumab in human epidermal growth factor receptor-2 (HER2)-positive early breast cancer (BC). Methods: In this multicenter, phase II study, patients with confirmed HER2-positive early BC received four cycles of PLD (30-35 mg/m2) and cyclophosphamide (600 mg/m2), followed by four cycles of taxanes (docetaxel, 90-100 mg/m2 or nab-paclitaxel, 260 mg/m2), concomitant with eight cycles of trastuzumab (8 mg/kg loading dose, then 6 mg/kg) and pertuzumab (840 mg loading dose, then 420 mg) every 3 weeks. The primary endpoint was total pathological complete response (tpCR, ypT0/is ypN0). Secondary endpoints included breast pCR (bpCR), objective response rate (ORR), disease control rate, rate of breast-conserving surgery (BCS), and safety (with a focus on cardiotoxicity). Results: Between May 27, 2020 and May 11, 2022, 78 patients were treated with surgery, 42 (53.8%) of whom had BCS. After neoadjuvant therapy, 47 [60.3%, 95% confidence interval (95% CI), 48.5%-71.2%] patients achieved tpCR, and 49 (62.8%) achieved bpCR. ORRs were 76.9% (95% CI, 66.0%-85.7%) and 93.6% (95% CI, 85.7%-97.9%) after 4-cycle and 8-cycle neoadjuvant therapy, respectively. Nine (11.5%) patients experienced asymptomatic left ventricular ejection fraction (LVEF) reductions of ≥10% from baseline, all with a minimum value of >55%. No treatment-related abnormal cardiac function changes were observed in mean N-terminal pro-BNP (NT-proBNP), troponin I, or high-sensitivity troponin. Conclusions: This dual HER2-blockade with sequential polychemotherapy showed promising activity with rapid tumor regression in HER2-positive BC. Importantly, this regimen showed an acceptable safety profile, especially a low risk of cardiac events, suggesting it as an attractive treatment approach with a favorable risk-benefit balance.

14.
Food Res Int ; 182: 114077, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38519167

RESUMO

Fruits flavor deterioration is extremely likely to occur during post-harvest storage, which not only damages quality but also seriously affects its market value. This work focuses on the study of fruits deterioration odorants during storage by describing their chemical compositions (i.e., alcohols, aldehydes, acids, and sulfur-containing compounds). Besides, the specific flavor deterioration mechanisms (i.e., fermentation metabolism, lipid oxidation, and amino acid degradation) inducing by factors (temperature, oxygen, microorganisms, ethylene) are summarized. Moreover, quality control strategies to mitigate fruits flavor deterioration by physical (temperature control, hypobaric treatment, UV-C, CA) and chemical (1-MCP, MT, NO, MeJA) techniques are also proposed. This review will provide useful references for fruits flavor control technologies development.


Assuntos
Frutas , Odorantes , Frutas/química , Aldeídos/análise , Álcoois/análise , Fermentação
15.
Comp Immunol Microbiol Infect Dis ; 107: 102157, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38484424

RESUMO

Trichomonas gallinae, a protozoan parasite causing avian trichomonosis, exhibits a widespread global prevalence. It primarily affects the upper digestive tract of birds and has resulted in significant ecological problems worldwide. This study aimed to investigate the prevalence and genotypes of T. gallinae in Anhui Province, China. A total of 1612 oropharyngeal swab samples were collected from pigeon farms in Anhui Province to determine the prevalence of T. gallinae infection. The results revealed 565 (35.1%) positive samples of T. gallinae. Significant differences in infection rates were observed among different regions and age groups. Furthermore, the ITS1/5.8 S/ITS2 region was amplified, sequenced, and subjected to phylogenetic analysis. Genotypes A and B of T. gallinae were identified, and genotype B was the dominant genotype in Anhui Province. This is the first report on the prevalence and molecular characterization of T. gallinae in Anhui Province, China. Additionally, we integrated reports on the prevalence and genotype of T. gallinae in relevant provinces in China.


Assuntos
Doenças das Aves , Trichomonas , Animais , Trichomonas/genética , Columbidae/parasitologia , Prevalência , Filogenia , Doenças das Aves/epidemiologia , Doenças das Aves/parasitologia , China/epidemiologia
16.
Int Ophthalmol ; 44(1): 148, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38502381

RESUMO

PURPOSE: To investigate corneal biomechanical properties and its associations with the severity of lens dislocation in patients with Marfan syndrome. METHODS: A total of 30 patients with Marfan syndrome and 30 age-, sex- and axial length (AL)-matched controls were recruited. Corneal biomechanical parameters of both groups were measured by CorVis ST and were compared between groups. Potential associations between corneal biomechanical parameters and severity of lens dislocation were also investigated. RESULTS: Lower applanation 1 velocity (A1V) (0.13 ± 0.004 vs. 0.15 ± 0.003, P = 0.016), shorter applanation 2 time (A2T)(22.64 ± 0.11 vs. 22.94 ± 0.11, P = 0.013), longer peak distance (PD) (5.03 ± 0.07 vs. 4.81 ± 0.05, P = 0.008), longer radius (R) of highest concavity (7.44 ± 0.16 vs. 6.93 ± 0.14, P = 0.012), greater Ambrosio relational thickness horizontal (ARTh) (603 ± 20 vs. 498 ± 12, P < 0.001), and integrated radius (IR) (8.32 ± 0.25 vs. 8.95 ± 0.21, P = 0.033) were detected among Marfan eyes compared with controls (all P < 0.05). Marfan individuals with more severe lens dislocation tended to have increased stiffness parameter as longer A1T, slower A1V, shorter A2T, slower application 2 velocity (A2V), smaller PD and smaller Distance Amplitude (DA) (P < 0.05). CONCLUSION: Marfan patients were detected to have increased corneal stiffness compared with normal subjects. Corneal biomechanical parameters were significantly associated with the severity of lens dislocation in Marfan patients.


Assuntos
Subluxação do Cristalino , Síndrome de Marfan , Humanos , Síndrome de Marfan/complicações , Síndrome de Marfan/diagnóstico , Pressão Intraocular , Fenômenos Biomecânicos , Córnea , Subluxação do Cristalino/diagnóstico , Subluxação do Cristalino/etiologia , Tonometria Ocular
18.
Gene Expr Patterns ; 51: 119356, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38432189

RESUMO

It can be observed from aminoglycoside-induced hair cell damage that the cochlea basal turn is more susceptible to trauma than the apex. Drug-induced hearing loss is closely related to oxidative damage. The basilar membrane directly exposed to these ototoxic drugs exhibits differences in damage, indicating that there is an inherent difference in the sensitivity to oxidative damage from the apex to the base of the cochlea. It has been reported that the morphology and characteristics of the cochlea vary from the apex to the base. Therefore, we investigated oxidative stress-related gene expression profiles in the apical, middle, and basal turns of the cochlea. The Oxidative Stress RT2 Profiler™ PCR Array revealed that three of the 84 genes (Mb, Mpo, and Ncf1) were upregulated in the middle turn compared to their level in the apical turn. Moreover, eight genes (Mb, Duox1, Ncf1, Ngb, Fmo2, Gpx3, Mpo, and Gstk1) were upregulated in the basal turn compared to their level in the apical turn. The qPCR verification data were similar to that of the PCR Array. We found that MPO was expressed in the rat cochlea and protected against gentamicin-induced hair cell death. This study summarized the data for the gradient of expression of oxidative stress-related genes in the cochlea and found potential candidate targets for prevention of ototoxic deafness, which may provide new insights for cochlear pathology.


Assuntos
Cóclea , Estresse Oxidativo , Ratos , Animais , Cóclea/metabolismo , Cóclea/patologia , Perfilação da Expressão Gênica , Morte Celular , Transcriptoma
19.
Food Chem ; 443: 138578, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38301554

RESUMO

Optimization of seven parameters of stir bar sorptive extraction (SBSE) on mulberry volatile components for the first time. A total of 347 volatile components were identified and quantified in 14 mulberry varieties, predominantly encompassing esters, aldehydes, terpenoids, hydrocarbons, ketones, alcohols, heterocyclics, acids, and phenols. Hexanal and (E)-2-hexenal were the dominant volatiles. Furthermore, 79 volatile compounds characterized by odor activity values (OAVs) > 1 were identified, making a significant contribution to the distinctive mulberry flavor. "Green" notes were the most intense, followed by "fatty" and "fruity". Utilizing odor ring charts, the volatile flavor characteristics of the 14 mulberry varieties could be intuitively distinguished. This study not only established a viable methodology for differentiating mulberry varieties but also laid a theoretical foundation for the quality evaluation and variety breeding of mulberry flavor.


Assuntos
Aldeídos , Morus , Compostos Orgânicos Voláteis , Compostos Orgânicos Voláteis/análise , Melhoramento Vegetal , Cromatografia Gasosa-Espectrometria de Massas/métodos , Frutas/química , Odorantes/análise
20.
Int Ophthalmol ; 44(1): 85, 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38363416

RESUMO

BACKGROUND: Congenital ectopia lentis (CEL) is a hereditary eye disease which severely impacts preschool children's visual function and development. This study aimed to evaluate the longitudinal changes in spherical equivalent (SE) refractive error in preschool children with CEL. METHODS: A retrospective cohort study was conducted at Zhongshan Ophthalmic Center, Guangzhou, China. Medical records of CEL patients under 6-year-old who were diagnosed with Marfan syndrome at the initial visit from January 2014 to March 2022 were collected and were divided into surgery and non-surgery groups. Mean change rate of SE in the two groups was evaluated, and the potential associated factors of SE change rate were investigated by mixed-effect regression model. RESULTS: A total of 94 preschool patients from 14 provinces of China were included. Among the 42 children of the surgery group, the mean age with standard deviation (SD) was 5.02 ± 0.81 years and patients experienced a myopic shift of -0.05 ± 0.09 D/month in average. The mean age with SD of the 52 children of the non-surgery group was 4.34 ± 1.02 years, and the mean myopic shift was -0.09 ± 0.14 D/month. The mixed-effect regression model identified that higher degree of myopia at baseline was associated with slower myopic shift both in surgery (ß = 0.901, 95% CI: 0.822 ~ 0.980, P < 0.001) and in non-surgery group (ß = 1.006, 95% CI: 0.977 ~ 1.034, P < 0.001) in CEL patients. Surgical treatment (ß = 2.635, 95% CI: 1.376 ~ 3.894, P < 0.001) was associated with slower myopic shift in all participants CEL patients. CONCLUSIONS: Myopic progression was slower in the surgery group than in the non-surgery group of CEL. Preschool CEL patients who met the surgical indication are suggested being performed with timely surgery to slow down the myopic progression.


Assuntos
Ectopia do Cristalino , Miopia , Erros de Refração , Humanos , Pré-Escolar , Criança , Refração Ocular , Ectopia do Cristalino/diagnóstico , Ectopia do Cristalino/cirurgia , Estudos Retrospectivos , Erros de Refração/diagnóstico , Miopia/diagnóstico
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