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BACKGROUND: Breast cancer (BC) remains a significant global health challenge, contributing substantially to cancer-related deaths worldwide. Its prevalence and associated death rates remain alarmingly high, highlighting the persistent public health burden. The objective of this study was to systematically examine the involvement of SUSD3 (Sushi Domain-Containing 3) in BC, highlighting its crucial role in the pathogenesis and progression of this disease. METHODS: BC-related gene microarray data, along with corresponding clinicopathological information, were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Leveraging TIMER and HPA databases, we conducted comparative analyses to evaluate SUSD3 expression in BC. We then analyzed the association between SUSD3 and clinical traits, as well as the prognostic value of SUSD3. SUSD3-related differential expression genes (DEGs) were sent for analysis utilizing GO, KEGG, and GSEA. We utilized SUSD3 mRNA expression to assess immune cells' scores in BC tissues calculated by single-sample enrichment analyses based on "CIBERSORT" R package. Drug sensitivity analysis was used to screen potential drugs sensitive to SUSD3. R software was used for statistical analyses and graphical representation of the data. RESULTS: Our findings confirmed a significant upregulation of SUSD3 expression in BC, which correlated with a favorable prognosis. Clinical correlation analysis further emphasized the strong association between SUSD3 expression and key clinical parameters like estrogen receptor (ER) status, progesterone receptor (PR) status, stage, and T classification in breast cancer. Univariate and multivariate Cox regression analyses showed that SUSD3 could be used as an independent prognostic factor for BC. Differentially expressed genes (DEGs) co-expressed with SUSD3 were significantly associated with various biological processes, such as the cell cycle, DNA replication, p53 signaling pathway, cancer-related pathways, and Wnt signaling pathway, as indicated by gene set enrichment analysis (GSEA). Furthermore, our analysis demonstrated that SUSD3 generally exhibited negative associations with immune modulators. Drug sensitivity analysis revealed positive correlations between SUSD3 and the efficacy of Fulvestrant, Raloxifene, and Fluphenazine. CONCLUSION: The research emphasizes the significance of SUSD3 as a potential marker for BC, providing insights into the underlying molecular mechanisms implicated in tumorigenesis. SUSD3 holds promise in helping the classification of breast cancer pathological groups, predicting prognosis, and facilitating targeted therapy.
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Background: A considerable controversy over performing thyroidectomy and central lymph node dissection in patients with papillary thyroid microcarcinoma (PTMC) remained. However, accurate prediction of central lymph node metastasis (CLNM) is crucial for surgical extent and proper management. The aim of this study was to develop and validate a practical nomogram for predicting CLNM in patients with PTMC. Methods: A total of 1,029 patients with PTMC who underwent thyroidectomy and central lymph node dissection at Tangdu Hospital (the Second Affiliated Hospital of Air Force Medical University) and Xijing Hospital (the First Affiliated Hospital of Air Force Medical University) were selected. Seven hundred and nine patients were assigned to the training set and 320 patients to the validation set. Data encompassing demographic characteristics, ultrasonography results, and biochemical indicators were obtained. Stepwise backward selection and multiple logistic regression were used to screen the variables and establish the nomogram. Concordance index (C-index), receiver operating characteristic (ROC) curve analysis, and decision curve analysis (DCA) were employed to evaluate the nomogram's distinguishability, accuracy, and clinical utility. Results: Young age, multifocality, bigger tumor, presence of microcalcification, aspect ratio (height divided by width) ≥1, loss of fatty hilum, high free thyroxine (FT4), and lower anti-thyroid peroxidase antibody (TPOAb) were significantly associated with CLNM. The nomogram showed strong predictive capacity, with a C-index and accuracy of 0.784 and 0.713 in the training set and 0.779 and 0.703 in the external validation set, respectively. DCA indicated that the nomogram demonstrated strong clinical applicability. Conclusions: We established a reliable, cost-effective, reproducible, and noninvasive nomogram for predicting CLNM in patients with PTMC. This tool could be a valuable guidance for deciding on management in PTMC.
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Background: Papillary thyroid cancer (PTC) is prevalent among younger populations and has a favorable survival rate. However, a significant number of patients experience psychosocial stress and a reduced quality of life (QoL) after surgical treatment. Therefore, comprehensive evaluations of the patients are essential to improve their recovery. Methods: The present study enrolled 512 young and middle-aged patients diagnosed with PTC who underwent surgery at our institution between September 2020 and August 2021. Each participant completed a series of questionnaires: Generalized Anxiety Disorder 7 (GAD-7), European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), Thyroid Cancer-Specific Quality of Life Questionnaire (THYCA-QoL), and Readiness to Return-to-Work Scale (RRTW). Results: GAD-7 data showed that almost half of the study subjects were experiencing anxiety. Regarding health-related quality of life (HRQoL), participants reported the highest levels of fatigue, insomnia, voice problems, and scarring, with patients in anxious states reporting worse symptoms. Based on RRTW, more than half of the subjects had returned to work and had better HRQoL compared to the others who were evaluating a possible return to work. Age, gender, BMI, education, diet, residence, health insurance, months since surgery, monthly income, and caregiver status were significantly correlated with return to work. Additionally, having a caregiver, higher monthly income, more time since surgery, and living in a city or village were positively associated with return to work. Conclusion: Young and middle-aged patients with PTC commonly experience a range of health-related issues and disease-specific symptoms following surgery, accompanied by inferior psychological well-being, HRQoL, and work readiness. It is crucial to prioritize timely interventions targeting postoperative psychological support, HRQoL improvement, and the restoration of working ability in PTC patients.
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Oral absorption of ginsenoside Rb1 (Rb1) is often hindered by the gastrointestinal tract. Carboxymethyl chitosan deoxycholic acid loaded with ginsenoside Rb1 nanoparticles (CMDA@Rb1-NPs), were prepared as a delivery system using a self-assembly technique with amphipathic deoxycholic acid grafted carboxymethyl chitosan as the carrier, which improved the stability and embedding rate of Rb1. In addition, the CMDA@Rb1-NPs was encapsulated with sodium alginate by ion crosslinking method with additional layer (CMDAlg@Rb1-NPs). Scanning electron microscopy showed that the nanoparticles were spherical, evenly distributed, smooth and without obvious adhesion. By evaluating drug loading, entrapment efficiency, the encapsulation efficiency of Rb1 increased from 60.07 % to 72.14 % after grafting deoxycholic acid improvement and optimization. In vitro release results showed that the cumulative release of Rb1 by CMDAlg-NPs showed a pH dependent effect, which was <10 % in simulated gastric juice with pH 1.2, completely released with pH 7.4 for about 48 h. In addition, Rb1 and CMDAlg@Rb1-NPs had inhibitory effects on A549 cells, and the inhibitory effect of CMDAlg@Rb1-NPs was better. Therefore, all results indicated that CMDA/Alg@Rb1 nanoparticles might be a novel drug delivery system to improve the stability and embedding rate of Rb1, and has the potential to be applied in oral pharmaceutical preparations.
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Quitosano , Portadores de Fármacos , Liberación de Fármacos , Ginsenósidos , Nanopartículas , Quitosano/química , Quitosano/análogos & derivados , Ginsenósidos/química , Ginsenósidos/farmacología , Ginsenósidos/farmacocinética , Concentración de Iones de Hidrógeno , Nanopartículas/química , Humanos , Portadores de Fármacos/química , Línea Celular Tumoral , Tamaño de la PartículaRESUMEN
Background: Cervical lymph node enlargement caused by coronavirus disease 2019 (COVID-19) vaccination has been reported, but little is known on whether the vaccination would influence preoperative cervical lymph node evaluation and its risk of lymph node metastasis in thyroid cancer. Methods: We retrospectively analyzed data of patients who underwent thyroid cancer surgery in Tangdu Hospital, China, from 1 March 2021 to 30 June 2021. A total of 182 patients were included in the cohort study. All patients with suspected malignant tumors underwent ultrasound (US)-guided fine needle aspiration (FNA) of thyroid lesions before surgery to confirm the diagnosis. Cervical lymph nodes were evaluated by preoperative physical examination and imaging. Wilcoxon rank-sum test and Fisher's exact test were used to evaluate the effect of vaccination on cervical lymph nodes in patients with thyroid cancer. Statistical significance was defined at P<0.05. Results: The patients were divided into two groups according to whether they had been vaccinated or not. Our results showed that there were no significant differences between the two groups in the brand of the vaccine, operation method, and the extent of surgery. Moreover, there was no significant difference in the evaluation of US characteristics of cervical lymph nodes between the two groups regardless of having the vaccination or not. Interestingly, US evaluation found that the experimental group's proportion of cervical lymph node enlargement increased significantly within 14 days after vaccination, which was statistically significant. Conclusions: This study found that vaccination against COVID-19 did not increase the number of cervical lymph node metastases, but inaccurate assessment of cervical lymph nodes in thyroid cancer patients within 14 days of vaccination (due to temporary lymph node enlargement) may lead to more extensive surgery.
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BACKGROUND: Simulation-based medical education (SBME) and three-dimensional printed (3DP) models are increasingly used in continuing medical education and clinical training. However, our understanding of their role and value in improving trainees' understanding of the anatomical and surgical procedures associated with liver surgery remains limited. Furthermore, gender bias is also a potential factor in the evaluation of medical education. Therefore, the aim of this study was to evaluate the educational benefits trainees receive from the use of novel 3DP liver models while considering trainees' experience and gender. METHODS: Full-sized 3DP liver models were developed and printed using transparent material based on anonymous CT scans. We used printed 3D models and conventional 2D CT scans of the liver to investigate thirty trainees with various levels of experience and different genders in the context of both small group teaching and formative assessment. We adopted a mixed methods approach involving both questionnaires and focus groups to collect the views of different trainees and monitors to assess trainees' educational benefits and perceptions after progressing through different training programs. We used Objective Structured Clinical Examination (OSCE) and Likert scales to support thematic analysis of the responses to the questionnaires by trainees and monitors, respectively. Descriptive analyses were conducted using SPSS statistical software version 21.0. RESULTS: Overall, a 3DP model of the liver is of great significance for improving trainees' understanding of surgical procedures and cooperation during operation. After viewing the personalized full-sized 3DP liver model, all trainees at the various levels exhibited significant improvements in their understanding of the key points of surgery (p < 0.05), especially regarding the planned surgical procedure and key details of the surgical procedures. More importantly, the trainees exhibited higher levels of satisfaction and self-confidence during the operation regardless of gender. However, with regard to gender, the results showed that the improvement of male trainees after training with the 3DP liver model was more significant than that of female trainees in understanding and cooperation during the surgical procedure, while no such trend was found with regard to their understanding of the base knowledge. CONCLUSION: Trainees and monitors agreed that the use of 3DP liver models was acceptable. The improvement of the learning effect for practical skills and theoretical understanding after training with the 3DP liver models was significant. This study also indicated that training with personalized 3DP liver models can improve all trainees' presurgical understanding of liver tumours and surgery and males show more advantage in understanding and cooperation during the surgical procedure as compared to females. Full-sized realistic 3DP models of the liver are an effective auxiliary teaching tool for SBME teaching in Chinese continuing medical education.
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Neoplasias , Sexismo , Humanos , Femenino , Masculino , Hígado/diagnóstico por imagen , Hígado/cirugía , Abdomen , Impresión TridimensionalRESUMEN
A series of chiral bifunctional organocatalysts were prepared and used for enantioselective synthesis of 3-substituted isoindolinones from 2-formylarylnitriles and malonates through aldol-cyclization rearrangement tandem reaction in excellent yields and enantioselectivites (up to 87% yield and 95% ee) without recrystallization. In this investigation, we found that chiral tertiary-amine catalysts with a urea group can afford 3-substituted isoindolinones both in higher yields (87% vs. 77%) and enantioselectivities (95% ee vs. 46% ee) than chiral bifunctional phase-transfer catalysts.
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BACKGROUND: Potassium voltage-gated channel subfamily Q member 1 (KCNQ1), is implicated in the onset and progression of gastric carcinoma (GC), one of the most common types of stomach malignancies. This research aims to investigate the potential prognostic implications of KCNQ1 mRNA in GC using various databases such as The Cancer Genome Atlas (TCGA), The Human Protein Atlas (HPA), LinkedOmics, TISIDB, ESTIMATE, and TIMER. METHODS: We searched the HPA database to obtain information on KCNQ1 levels in human normal tissues, organs, and cell lines as well as in pan-cancer tissues. Then, we used TIMER and UALCAN to comparatively analyze the KCNQ1 mRNA levels in different types of cancers relative to their adjacent normal counterparts. Based on TCGA and Gene Expression Omnibus, the correlation of clinical information with KCNQ1 expression was analyzed using logistic regression model. Univariable and Multivariate Cox analyses were then carried out to compare differences in survival among patients with different clinical characteristics. The multivariate methods, such as Kaplan-Meier plotter and GEPIA survival curves, were further employed to identify the correlation of KCNQ1 expression with overall survival (OS). Besides, LinkedOmics was used to identify differentially expressed genes for functional enrichment analysis. RESULTS: KCNQ1 exhibited tissue-specific imprinting and expression in human normal tissues, organs and cell lines, while it was aberrantly expressed in pan-cancer tissues. Lower KCNQ1 mRNA expression was determined in GC tissue samples versus normal counterparts. In GC cases, elevated KCNQ1 levels were strongly linked to a longer OS and strongly correlated with invasion depth (χ2=12.631, P=0.006), TNM stage (χ2=8.750, P=0.033), differentiation grade (χ2=7.426, P=0.024), and vital status (χ2=5.676, P=0.017). Furthermore, KCNQ1 was identified by univariable and multivariate Cox analyses as an independent risk factor for GC. Based on Gene Ontology analysis, digestion as well as tricarboxylic acid metabolic, carbohydrate catabolic, and small molecule catabolic processes were differentially enriched in the up-regulated KCNQ1 phenotypic pathway. While carbon metabolism, fatty acid degradation, peroxisome, and citrate cycle (TCA cycle) were identified by the Kyoto Encyclopedia of Genes and Genomes-based analysis as pathways with differential enrichment. CONCLUSION: Being a prognostic biomarker, KCNQ1 may play an inhibitory role and involve in the metabolic process of GC.
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Ferroptosis, being classified as a form of regulated cell death, was driven by the oxidative injury induced by lipid peroxidation (LPO). Recently, ferroptosis has been confirmed to exert a critical effect in the pathogenesis and treatment of various tumors, including gastric cancer (GC). Erastin, as a frequently used ferroptosis inducer, caused ferroptosis by downregulating the xCT expression resulting in increasing reactive oxygen species (ROS) and aggravating the LPO. However, the mechanisms of Erastin in ferroptosis regulation, especially in GC, remain largely elusive. This work firstly demonstrated that Erastin inhibited cell growth and promoted apoptosis and ferroptosis in AGS and BGC823 cells. Then, based on Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of Erastin-related targets screened by using PharmMapper Web, the P38MAPK signaling was explored and validated in AGS and BGC-823 cells. Besides, the Fer-1 and P38 inhibitor were performed to investigate the mechanisms of ferroptosis induced by Erastin in depth. This work revealed a feedback mode among xCT, ROS and the P38MAPK pathway, which affected each other. It meant that Erastin regulated ferroptosis through the xCT-mediated ROS/P38MAPK signaling feedback loop. In addition, it was noticed that in co-operation with Erastin, the cytotoxic effects of Afatinib on cells were aggravated by further strengthening ferroptosis with activation of the P38MAPK pathway. In summary, those works provided evidence that Erastin plays an important role in increasing the cytotoxic effect on GC cells treated with Afitinib. Furthermore, the Erastin-induced ferroptosis via the xCT-mediated ROS/P38MAPK pathway feedback loop provides new strategies for GC comprehensive treatment.
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Neoplasias Gástricas , Humanos , Especies Reactivas de Oxígeno/metabolismo , Afatinib , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/genética , RetroalimentaciónRESUMEN
BACKGROUND: HER2-low could be found in some patients with triple-negative breast cancer (TNBC). However, its potential impacts on clinical features and tumor biological characteristics in TNBC remain unclear. METHODS: We enrolled 251 consecutive TNBC patients retrospectively, including 157 HER2-low (HER2low) and 94 HER2-negtive (HER2neg) patients to investigate the clinical and prognostic features. Then, we performed single-cell RNA sequencing (scRNA-seq) with another seven TNBC samples (HER2neg vs. HER2low, 4 vs. 3) prospectively to further explore the differences of tumor biological properties between the two TNBC phenotypes. The underlying molecular distinctions were also explored and then verified in the additional TNBC samples. RESULTS: Compared with HER2neg TNBC, HER2low TNBC patients exhibited malignant clinical features with larger tumor size (P = 0.04), more lymph nodes involvement (P = 0.02), higher histological grade of lesions (P < 0.001), higher Ki67 status (P < 0.01), and a worse prognosis (P < 0.001; HR [CI 95%] = 3.44 [2.10-5.62]). Cox proportional hazards analysis showed that neoadjuvant systemic therapy, lymph nodes involvement and Ki67 levels were prognostic factors in HER2low TNBC but not in HER2neg TNBC patients. ScRNA-seq revealed that HER2low TNBC which showed more metabolically active and aggressive hallmarks, while HER2neg TNBC exhibited signatures more involved in immune activities with higher expressions of immunoglobulin-related genes (IGHG1, IGHG4, IGKC, IGLC2); this was further confirmed by immunofluorescence in clinical TNBC samples. Furthermore, HER2low and HER2neg TNBC exhibited distinct tumor evolutionary characteristics. Moreover, HER2neg TNBC revealed a potentially more active immune microenvironment than HER2low TNBC, as evidenced by positively active regulation of macrophage polarization, abundant CD8+ effector T cells, enriched diversity of T-cell receptors and higher levels of immunotherapy-targeted markers, which contributed to achieve immunotherapeutic response. CONCLUSIONS: This study suggests that HER2low TNBC patients harbor more malignant clinical behavior and aggressive tumor biological properties than the HER2neg phenotype. The heterogeneity of HER2 may be a non-negligible factor in the clinical management of TNBC patients. Our data provide new insights into the development of a more refined classification and tailored therapeutic strategies for TNBC patients.
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Neoplasias de la Mama , Neoplasias de la Mama Triple Negativas , Humanos , Femenino , Neoplasias de la Mama Triple Negativas/terapia , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Antígeno Ki-67 , Estudios Retrospectivos , Pronóstico , Microambiente Tumoral/genéticaRESUMEN
Background: It has been established that clusterin is involved in the invasion of immune cells in the tumor microenvironment, but it remains unknown how it promotes immune invasion in breast cancer. Methods: We used Tumor Immune Estimation Resource (TIMER) and Gene Expression Profiling Interactive Analysis (GEPIA) databases to assess the relation between expression of clusterin and immunoinfiltration-related marker genes. TIMER database was used to evaluate the expression of clusterin, and its relation to tumor immune invasion was examined. Based on Kaplan-Meier plotter database, we investigated the association between clusterin expression and prognosis in patients with cancer, and the impact of clinicopathological factors and cancer-related outcomes. Results: Clusterin expression was markedly associated with prognosis of a variety of tumors, specifically breast cancer. Enhanced clusterin expression was markedly associated with molecular typing of breast cancer and expression of multiple markers related to specific immune cell subsets. Conclusions: These results indicate that clusterin is connected to prognosis of breast cancer patients and tumor immune cell infiltration. This demonstrates that clusterin may be a biomarker of immune cell recruitment into breast tumors and an important biomarker for immune cell infiltration; consequently being a valuable prognostic factor in breast cancer patients.
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Background: Most patients with papillary thyroid carcinoma have a good prognosis. Excessive resection of thyroid and cervical lymph nodes is an important reason for affecting the quality of life of patients after surgery. Intraoperative rapid frozen pathological examination is an important step in the development of a surgical plan for thyroid cancer (especially micropapillary carcinoma); however, whether it affects the treatment outcome remains unclear. Methods: The clinicopathological data of papillary thyroid microcarcinoma (PTMC) patients who underwent surgery in our center from 1 January 2021 to 31 December 2021 were retrospectively analyzed. Patients with unilateral low-risk PTMC who underwent radical surgery were selected as the main research subjects. The negative results of intraoperative frozen section of the central lymph node (CLN) of the affected side were the experimental group, and the positive results were the control group. Subjects with lesions larger than 10 mm and those who did not undergo intraoperative frozen section pathological examination were excluded. After excluding other risk factors for recurrence, we calculated the proportion of patients requiring radioactive iodine (RAI) treatment among those with metastases detected by intraoperative rapid frozen section pathology and its influencing factors. Patient data were analysed using SPSS version 20. Continuous variables were presented as means when symmetrical or as medians and ranges when asymmetrical. Categorical variables were presented as proportions. A P value <0.05 was considered significant. Results: A total of 564 PTMC patients were included, among whom 122 patients (21.6%) underwent total thyroidectomy due to the presence of metastases in the ipsilateral CLNs. Compared with the experimental group, the patients with male, young age and tumor located in the middle and lower pole in the control group had higher lymph node metastasis (P<0.05). Conclusions: The proportion of patients requiring postoperative RAI treatment for unilateral low-risk PTMC is relatively low, and the possibility that an intraoperative frozen pathological finding will change the treatment outcome is low. However, the need for postoperative RAI therapy notably increases when the intraoperative frozen pathological analysis reveals ipsilateral CLN metastases, especially in males, younger patients, and/or patients with lesions located in the middle and lower poles.
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Background: Recently, increasing literature has been reported on optimal therapies in patients with advanced hepatocellular carcinoma (HCC) and many therapeutic modalities have been proposed to improve the survival rate. However, the results are not consistent due to different research protocols, small sample sizes and different study endpoints and there is no standard treatment protocol has been defined. Therefore, it is very important to explore the optimal bonding mode and to evaluate the efficacy and safety of the optimal sequential therapy for those patients. Methods: We searched available databases through January 2020 for relevant studies. The main outcome measure was 1-year overall survival (OS) and overall response rate (ORR); the secondary outcome measure was a composite of toxic effects retrieved grade 3 or 4 adverse events (AEs) from all included studies. Statistical analyses were conducted using STATA version 15 and GeMTC package in the R statistical software. Results: After a detailed review, 8 randomized controlled trials (RCTs) and 20 retrospective studies involving 3,675 advanced HCC patients were included for network meta-analysis. Indirect comparisons showed that hepatic arterial infusion chemotherapy (HAIC) plus radiofrequency ablation (RFA) was highest probability of obtaining the best OS rate of 1 year [surface under the cumulative ranking (SUCRA), 0.95] and ORR (SUCRA, 0.86) when compared with other potential optimal therapies and which had ranked the first in all treatment regimens, followed by HAIC (SUCRA, 0.75). Direct and indirect comparison of 1-year OS and ORR with all treatment regimens each other showed that for all treatment regimens, patients showed significant clinical benefit when compared with transcatheter arterial chemoembolization (TACE) or sorafenib alone. However, the incidence of treatment-related AEs of grade 3 or 4 occurred in patients who have received targeted drug sorafenib therapy (SUCRA, 0.51) compared with other interesting regimens. Conclusions: HAIC may be a valuable therapeutic strategy for advanced HCC patients to prevent recurrence and metastasis after RFA, as well as in improving patient prognosis and quality of life. Meanwhile, HAIC combined with RFA is a safe and effective treatment in patients with advanced HCC, and this combination therapy can significantly prolong 1-year survival rate when compared with other optimal sequential therapies. Trial registration: This study is registered with PROSPERO, number CRD42020176149.
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Papillary thyroid carcinoma (PTC) has a high incidence, and its proper treatment remains challenging. Therefore, identifying PTC progression markers is essential. Here, using 16S RNA sequences, we analyzed the PTC intratumor microbiome and its role in tumor progression. Substantial microbial abundance was detected in PTC from all patients. The tumor bacterial diversity in patients with advanced lesions (T3/T4) was significantly higher than that in patients with relatively mild lesions (T1/T2). Importantly, we identified signatures of eight tumor bacterial taxa highly predictive of PTC invasion status. Hence, microbial host factors-independent of the genomic composition of the tumor-may determine tumor behaviors and patient outcomes. Furthermore, the correlation between specific bacterial genus and thyroid hormones or autoimmune thyroid disease-related antibodies may indicate the potential contribution of the microbiome in the relationship between autoimmune thyroid disease or irregular thyroid function and PTC progression, intervention of which might therefore be worth exploring for advancing oncology care.
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Carcinoma Papilar , Microbiota , Neoplasias de la Tiroides , Carcinoma Papilar/genética , Carcinoma Papilar/patología , Humanos , Procesos Neoplásicos , Cáncer Papilar Tiroideo/genética , Cáncer Papilar Tiroideo/patología , Neoplasias de la Tiroides/epidemiología , Neoplasias de la Tiroides/genética , Neoplasias de la Tiroides/patologíaRESUMEN
Background: In recent years, rectal foreign bodies have become a common proctological emergency in the male population, especially older Chinese men, often requiring surgical intervention due to associated complications. This review aimed to describe the epidemiology and clinical characteristics of rectal foreign bodies in older men and examine the possible challenges presented by the condition to clinicians and society. Methods: A comprehensive search was conducted in English-language databases and Chinese databases from January 2000 to December 2020. Studies concerning rectal foreign bodies were considered for this review if they reported the reason for a foreign body being in the rectum and related treatment measures. Contemporaneous rectal foreign bodies case data from General Surgery Department of Tangdu Hospital were also analyzed. According to differences in ethnicity, the older male patients were divided into a Chinese group and a non-Chinese group, and the parameters of the two groups were analyzed using statistical methods. Results: A total of 159 studies were retrieved in an initial database search using "rectal foreign body" as the search term. These included 86 Chinese studies and 73 English-language studies. Collectively, these studies included 582 older male patients, 276 of whom were Chinese, and 307 who were non-Chinese. According to their source, the rectal foreign bodies were classified into 3 categories. The most common reason for a foreign body in the rectum was insertion for erotic purposes, with everyday articles accounting for most foreign body types. Sexual articles were mainly found to have been used in the pursuit of pleasure. There were no significant differences in foreign body sources, sizes, types, treatment selections, and outcomes between the two groups. Discussion: Emergency hospital visits by older men with rectal foreign bodies due to erotic and sexual needs and practices are increasing. Although the sources, sizes, and types of foreign bodies were different, and patients recovered well after active and appropriate clinical treatment, the sexual needs of older men are a social issue that requires attention. Acknowledging and dealing with sexual issues is a multidimensional task that requires a collaborative effort to ensure a more humanistic approach to older patients.
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Background: Extrachromosomal circular DNA (eccDNA) is omnipresent in cancers and related to the progression of tumors and oncogene amplification. However, its function in breast cancer (BC) is unclear. Methods: After constructing the DNA library, CLeavage Effects by Circularization for In vitro Reporting of sequencing was performed for eccDNA detection using 1 BC tissue sample. Fastqc was used to evaluate the quality of the original data. Burrows-Wheeler-Alignment Tool was used to compare the original data to the reference genome. A Circle-MAP was subsequently performed to detect eccDNA, and Bedtools was used to annotate the eccDNA genes. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were conducted by ClusterProfiler. The Genotype-Tissue Expression and the Cancer Genome Atlas databases were used to collect the ribonucleic acid-sequencing data of the BC and normal samples. A Gene Expression Profiling Interactive Analysis, the University of Alabama at Birmingham CANcer data analysis Portal, and Kaplan-Meier survival curves were used to analyze the Cancer Genome Atlas data. Results: A total of 200 eccDNA genes, including IGTB7, were obtained. About the biological processes (BPs), these 200 genes were mainly enriched in actin cytoskeleton reorganization and axon guidance. Concerning the molecular functions (MFs), these 200 genes were mainly enriched in sodium ion transmembrane transporter activity and metal ion transmembrane transporter activity. As for cellular components (CCs), these 200 genes were mainly enriched in the transcription regulator complex and focal adhesion. ITGB7 was significantly enriched in cell-matrix adhesion and localization within the membrane in the BPs, integrin binding in the MFs, and cell-substrate junction and focal adhesion in the CCs. The 200 eccDNA genes were mainly enriched in the PI3K-Akt signaling pathway and focal adhesion. Notably, ITGB7 was enriched in focal adhesion, ECM-receptor interaction, the PI3K-Akt signaling pathway, and human papillomavirus infection. Besides, ITGB7 was significantly upregulated in BC patients and was associated with the menopause status of the BC patients. Conclusions: ITGB7 might serve as a prognostic marker for BC patients. ITGB7 has important implications for the individualized clinical treatment of BC patients.
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BACKGROUND: Pegylated liposomal doxorubicin (PLD) is an improved formulation of doxorubicin with comparable effectiveness but significantly lower cardiotoxicity than conventional anthracycline. This study aimed to evaluate the real-world effectiveness and safety of PLD versus epirubicin as neoadjuvant or adjuvant treatment for breast cancer. METHODS: Clinical data of invasive breast cancer patients who received neoadjuvant or adjuvant chemotherapy with PLD or epirubicin were retrospectively collected. Propensity score matching (PSM) was performed to reduce the risk of selection bias. The molecular typing of these patients included Luminal A, Luminal B, HER2-positive, and basal-like/triple-negative. The primary outcome was pathological complete response (pCR) rate for neoadjuvant chemotherapy and 3-year disease-free survival (DFS) rate for adjuvant chemotherapy. Noninferiority was suggested if the lower limit of the 95% CI for the 3-year DFS rate difference was greater than - 10%. The secondary outcome was adverse reactions. RESULTS: A total of 1213 patients were included (neoadjuvant, n = 274; adjuvant, n = 939). pCR (ypT0/Tis ypN0) rates of patients who received neoadjuvant chemotherapy were 11.6% for the PLD group and 7.0% for the epirubicin group, but the difference was not statistically significant (P = 0.4578). The 3-year DFS rate of patients who received adjuvant chemotherapy was 94.9% [95%CI, 91.1-98.6%] for the PLD group and 95.4% [95%CI, 93.0-97.9%] for the epirubicin group (P = 0.5684). Rate difference between the two groups and its 95% CI was - 0.55 [- 5.02, 3.92]. The lower limit of the 95% CI was - 5.0% > - 10.0%, suggesting that PLD is not be inferior to epirubicin in adjuvant chemotherapy for breast cancer. The incidences of myelosuppression, decreased appetite, alopecia, gastrointestinal reactions, and cardiotoxicity were lower in the PLD group than in the epirubicin group, while the incidence of nausea was higher in the PLD group. CONCLUSIONS: In the neoadjuvant and adjuvant treatment of breast cancer, effectiveness is similar but toxicities are different between the PLD-containing regimen and epirubicin-containing regimen. Therefore, further study is warranted to explore PLD-based neoadjuvant and adjuvant chemotherapy for breast cancer.
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Neoplasias de la Mama/tratamiento farmacológico , Quimioterapia Adyuvante/métodos , Doxorrubicina/análogos & derivados , Epirrubicina/uso terapéutico , Terapia Neoadyuvante/métodos , Adulto , Neoplasias de la Mama/patología , Supervivencia sin Enfermedad , Doxorrubicina/farmacología , Doxorrubicina/uso terapéutico , Epirrubicina/farmacología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Polietilenglicoles/farmacología , Polietilenglicoles/uso terapéuticoRESUMEN
Emphysematous splenic infection is a rare disease. In this case, a 33-year-old woman presented to the emergency department with a 10-day history of left-upper-quadrant abdominal pain and intermittent fever. She positively denied any previous history of illness or trauma. On admission to the hospital, her white-cell count, neutrophil percentage, C-reactive protein level, blood glucose, and urine glucose were higher than normal. Computed tomography (CT) revealed gas-fluid levels and infection in the spleen. After multidisciplinary consultation and discussions, the patient was diagnosed with emphysema spleen infection and diabetes, and the infection was most likely related to the diabetes. The patient was treated with antibiotics, hypoglycemic therapy, and transabdominal spleen infection puncture and drainage. Finally, the patient's infection and blood sugar were controlled, and the drainage fluid was unobstructed. To the best of our knowledge, emphysematous spleen infection has only been reported once previously in a super obese female patient in 2007. Interestingly, the patient in the present case was also an obese and diabetic middle-aged woman. Similar to other documented emphysematous infection cases, the disease onset of our patient was indistinct and insidious. Due to advances in imaging tools and knowledge of emphysematous nephritis, the patient was successfully diagnosed and treated in time.
Asunto(s)
Diabetes Mellitus , Enfisema , Adulto , Antibacterianos/uso terapéutico , Drenaje , Enfisema/tratamiento farmacológico , Enfisema/etiología , Femenino , Humanos , Persona de Mediana Edad , Tomografía Computarizada por Rayos XRESUMEN
BACKGROUND: Gastric cancer (GC) is one of the most significant health problems worldwide. Some studies have reported associations between Phospholipase C epsilon 1 (PLCE1) single-nucleotide polymorphisms (SNPs) and GC susceptibility, but its relationship with GC prognosis lacked exploration, and the specific mechanisms were not elaborated fully yet. This study aimed to further explore the possible mechanism of the association between PLCE1 polymorphisms and GC. MATERIALS AND METHODS: A case-control study, including 588 GC patients and 703 healthy controls among the Chinese Han population, was performed to investigate the association between SNPs of PLCE1 and GC risk by logistic regression in multiple genetic models. The prognostic value of PLCE1 in GC was evaluated by the Kaplan-Meier plotter. To explored the potential functions of PLCE1, various bioinformatics analyses were conducted. Furthermore, we also constructed the spatial structure of PLCE1 protein using the homology modeling method to analyze its mutations. RESULTS: Rs3765524 C > T, rs2274223 A > G and rs3781264 T > C in PLCE1 were associated with the increased risk of GC. The overall survival and progression-free survival of patients with high expression of PLCE1 were significantly lower than those with low expression [HR (95% CI) = 1.38 (1.1-1.63), P < 0.01; HR (95% CI) = 1.4 (1.07-1.84), P = 0.01]. Bioinformatic analysis revealed that PLCE1 was associated with protein phosphorylation and played a crucial role in the calcium signal pathway. Two important functional domains, catalytic binding pocket and calcium ion binding pocket, were found by homology modeling of PLCE1 protein; rs3765524 polymorphism could change the efficiency of the former, and rs2274223 polymorphism affected the activity of the latter, which may together play a potentially significant role in the tumorigenesis and prognosis of GC. CONCLUSION: Patients with high expression of PLCE1 had a poor prognosis in GC, and SNPs in PLCE1 were associated with GC risk, which might be related to the changes in spatial structure of the protein, especially the variation of the efficiency of PLCE1 in the calcium signal pathway.
RESUMEN
Gastric cancer (GC) is one of the most common malignancies, and its incidence rates vary widely between men and women. Previous studies have suggested that connexin 43 (Cx43, encoded by gap junction protein alpha 1 (GJA1)) and secretory carrier membrane protein 1 (SCAMP1) are key functional proteins in tumors. Herein, the association between GJA1 and SCAMP1 polymorphisms and GC susceptibility and prognosis was evaluated. A total of three single-nucleotide polymorphisms among 681GC patients and 756 controls were tested using the Agena MassARRAY RS1000 system, including GJA1 rs2071165, SCAMP1 rs4530741, and SCAMP1 rs6874309. The strength of the association with GC risk was assessed by the odds ratios (ORs) and 95% confidence intervals (CIs) generated from the logistic regression model. Kaplan-Meier curve, long-rank tests, and a multivariate Cox proportional hazard model were used for prognosis analysis. The expression of GJA1 was assessed by immunohistochemistry. The GJA1 rs2071165 AA/AG genotype significantly increased the risk of GC in the female Chinese population (OR = 1.55, 95% CI = 1.03-2.32, p=0.034). Furthermore, the risk effect of GJA1 rs2071165 was more evident in the subgroups of female patients with GC, stratified by age, clinical stage, tumor size, and recurrence/metastasis. However, no obvious differences in Cx43 expression in GC tissues were observed between males and females. Furthermore, no significant association between SCAMP1 rs4530741 and rs6874309 polymorphisms and GC risk or prognosis was observed. In conclusion, this study suggests for the first time that the GJA1 rs2071165 polymorphism is associated with increased GC risk in females, revealing a potential new clinical marker for assessing GC risk in females.