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2.
Heliyon ; 10(10): e30992, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38818187

RESUMO

Background: The effects of metformin on atrial fibrillation (AF) in type 2 diabetes patients remain unclear. We aimed to explore the effects of metformin on AF, including new-onset AF and AF burden, in type 2 diabetes patients with pacemakers. Methods and results: This retrospective study included a total of 227 patients. Based on the presence of paroxysmal AF, the patients were divided into a paroxysmal AF group (n = 80) and a non-AF group (n = 147). In the non-AF group, a significant association was observed between metformin use and a lower risk of new-onset AF in multivariable Cox hazards models (hazard ratio [HR]: 0.36; 95 % confidence interval [CI]: 0.14-0.91; p = 0.0311*) when adjusted for age, sex, body mass index (BMI), drinking, smoking, left atrial dimension, creatinine, complications, and drugs. In the paroxysmal AF group, univariable analysis indicated no association between the AF burden and metformin use (p = 0.817). Furthermore, when adjusted for metformin use, age, sex, BMI, drinking, smoking, cardiovascular disease, myocardial infarction, heart failure, stroke, and ejection fraction in multivariable Cox hazards models, we found a lower proportion of major adverse cardiovascular events (MACEs) both in the total (HR: 0.28; 95 % CI: 0.1-0.82; p = 0.0202*) and the non-AF group (HR: 0.19; 95 % CI: 0.05-0.79; p = 0.0223*) compared to that in the AF group (HR: 0.31; 95 % CI: 0.02-4.41; p = 0.3879). Conclusion: In type 2 diabetes patients with pacemakers, metformin reduced the probability of new-onset AF instead of addressing the AF burden. Furthermore, metformin therapy decreased the incidence of MACEs in type 2 diabetes patients without AF.

3.
J Gastrointest Surg ; 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38705366

RESUMO

BACKGROUND: This study presented an innovative technique in totally laparoscopic total gastrectomy (TLTG) for overlap esophagojejunostomy (E-J), termed self-pulling and latter transection (SPLT) (overlap SPLT). It evaluated the effectiveness and short-term outcomes of this novel method through a comparative analysis with the established functional end-to-end (FETE) E-J incorporating SPLT. METHODS: From September 2018 to September 2023, this study enrolled 68 patients with gastric cancer who underwent TLTG with overlap SPLT anastomosis and 120 patients who underwent TLTG with FETE SPLT anastomosis. Clinicopathologic characteristics and surgical and postoperative outcomes data for overlap SPLT cases were gathered and retrospectively compared with those from FETE SPLT TLTG to evaluate the effectiveness and clinical safety. RESULTS: The duration of anastomosis for overlap SPLT was 25.3 ± 7.4 minutes, significantly longer than that for the FETE SPLT (18.1 ± 4.0 minutes, P = .031). Perioperatively, 1 anastomosis-related complication occurred in each group, but this did not constitute a statistically significant difference (P = .682). No statistically significant differences were found between the 2 groups in terms of operative time, postoperative hospital stay, operative cost, surgical margins, or number of lymph nodes removed. Postoperative morbidity rates were similar between the groups (4.4% vs 5.8%, P = .676). CONCLUSION: The overlap SPLT technique is regarded as a safe and feasible method for anastomosis. There were no apparent differences in complications between overlap SPLT and FETE SPLT, but overlap SPLT costed 1 additional stapler cartridge and required a longer duration.

5.
Adv Healthc Mater ; 13(5): e2302927, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37986024

RESUMO

The global pandemic presents a critical threat to humanity, with no effective rapid-response solutions for early-stage virus dissemination. This study aims to create an AI-driven entry-blocker design system (AIEB) to fabricate inhalable virus-like nanocatchers (VLNCs) fused with entry-blocking peptides (EBPs) to counter pandemic viruses and explore therapeutic applications. This work focuses on developing angiotensin-converting enzyme 2 (ACE2)-mimic domain-fused VLNCs (ACE2@VLNCs) using AIEB and analyzing their interaction with the SARS-CoV-2 receptor binding domain (RBD), demonstrating their potential to hinder SARS-CoV-2 infection. Aerosol-based tests show ACE2@VLNCs persist over 70 min in the air and neutralize pseudoviruses within 30 min, indicating their utility in reducing airborne virus transmission. In vivo results reveal ACE2@VLNCs mitigate over 67% of SARS-CoV-2 infections. Biosafety studies confirm their safety, causing no damage to eyes, skin, lungs, or trachea, and not eliciting significant immune responses. These findings offer crucial insights into pandemic virus prevention and treatment, highlighting the potential of the ACE2@VLNCs system as a promising strategy against future pandemics.


Assuntos
Enzima de Conversão de Angiotensina 2 , COVID-19 , Humanos , Enzima de Conversão de Angiotensina 2/química , Enzima de Conversão de Angiotensina 2/metabolismo , SARS-CoV-2/fisiologia , Peptídeos/metabolismo , Inteligência Artificial , Ligação Proteica
6.
Mol Carcinog ; 63(2): 286-300, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37888201

RESUMO

Bladder cancer is a common kind of urinary system cancer, in which bladder urothelial carcinoma (BLCA) comprises approximately 90% of all bladder cancer types. In our previous study, we discovered KLHDC7B in urine exosomal messenger RNA (mRNA) as a prospective molecular marker for bladder cancer detection. To systematically study the role and mechanism of KLHDC7B in BLCA, we focused on the most common type of BLCA in this study. First, we used RNA sequencing to discover that KLHDC7B was considerably increased in BLCA patients' urine exosomes compared to healthy controls. Then, we validated this result in an independent cohort and identified it as an effective tool for diagnosing and distinguishing high-grade and low-grade BLCA. Finally, we studied the role and mechanism of KLHDC7B in BLCA at the cellular level, providing a functional basis for its expression as a novel laboratory diagnostic biomarker for BLCA exosomal mRNA, which has important theoretical and clinical significance.


Assuntos
Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Humanos , Apoptose/genética , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Carcinoma de Células de Transição/patologia , Proliferação de Células/genética , RNA Mensageiro/genética , Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologia
7.
Curr Med Sci ; 43(6): 1133-1150, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38015361

RESUMO

OBJECTIVE: Pseudogenes are initially regarded as nonfunctional genomic sequences, but some pseudogenes regulate tumor initiation and progression by interacting with other genes to modulate their transcriptional activities. Olfactory receptor family 7 subfamily E member 47 pseudogene (OR7E47P) is expressed broadly in lung tissues and has been identified as a positive regulator in the tumor microenvironment (TME) of lung adenocarcinoma (LUAD). This study aimed to elucidate the correlation between OR7E47P and tumor immunity in lung squamous cell carcinoma (LUSC). METHODS: Clinical and molecular information from The Cancer Genome Atlas (TCGA) LUSC cohort was used to identify OR7E47P-related immune genes (ORIGs) by weighted gene correlation network analysis (WGCNA). Based on the ORIGs, 2 OR7E47P clusters were identified using non-negative matrix factorization (NMF) clustering, and the stability of the clustering was tested by an extreme gradient boosting classifier (XGBoost). LASSO-Cox and stepwise regressions were applied to further select prognostic ORIGs and to construct a predictive model (ORPScore) for immunotherapy. The Botling cohorts and 8 immunotherapy cohorts (the Samstein, Braun, Jung, Gide, IMvigor210, Lauss, Van Allen, and Cho cohorts) were included as independent validation cohorts. RESULTS: OR7E47P expression was positively correlated with immune cell infiltration and enrichment of immune-related pathways in LUSC. A total of 57 ORIGs were identified to classify the patients into 2 OR7E47P clusters (Cluster 1 and Cluster 2) with distinct immune, mutation, and stromal programs. Compared to Cluster 1, Cluster 2 had more infiltration by immune and stromal cells, lower mutation rates of driver genes, and higher expression of immune-related proteins. The clustering performed well in the internal and 5 external validation cohorts. Based on the 7 ORIGs (HOPX, STX2, WFS, DUSP22, SLFN13, GGCT, and CCSER2), the ORPScore was constructed to predict the prognosis and the treatment response. In addition, the ORPScore was a better prognostic factor and correlated positively with the immunotherapeutic response in cancer patients. The area under the curve values ranged from 0.584 to 0.805 in the 6 independent immunotherapy cohorts. CONCLUSION: Our study suggests a significant correlation between OR7E47P and TME modulation in LUSC. ORIGs can be applied to molecularly stratify patients, and the ORPScore may serve as a biomarker for clinical decision-making regarding individualized prognostication and immunotherapy.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Carcinoma de Células Escamosas , Neoplasias Pulmonares , Humanos , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/terapia , Pulmão , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/terapia , Pseudogenes/genética , Microambiente Tumoral/genética
8.
Aging (Albany NY) ; 15(22): 13059-13076, 2023 11 17.
Artigo em Inglês | MEDLINE | ID: mdl-37980168

RESUMO

BACKGROUND: Ubiquitin fold modifier 1 (UFM1) overexpression is associated with cancer cell proliferation, migration and invasion. However, the roles and pathways of UFM1 in oral squamous cell carcinoma (OSCC) has remained undefined. METHODS: The expression of UFM1 and the relationship between UFM1 expression and prognosis were investigated using data of OSCC patients from The Cancer Genome Atlas (TCGA) database. The UFM1 co-expressed genes, and the association between the UFM1 expression and immune cells and ubiquitination were explored. The effects of UFM1 expression on the growth and migration of OSCC cells were investigated by siRNA interference, Cell Counting Kit-8 (CCK-8), Transwell, Western blotting, and wound healing experiments. RESULTS: UFM1 was highly expressed in OSCC. UFM1 overexpression was associated with short overall survival, disease-specific survival, and progression-free interval, and was an adverse factor for prognosis in OSCC. UFM1-related nomograms were significantly associated with poor prognosis in OSCC patients. Decreased UFM1 expression could inhibit the proliferation, migration, and invasion of OSCC cells. UFM1 was associated with the immune cells (such as the Th17 cells, T helper cells, and cytotoxic cells) and ubiquitination. CONCLUSION: Elevated UFM1 expression was associated with poor prognosis, ubiquitination and immune infiltration in OSCC, and inhibition of UFM1 expression delayed OSCC progression, showing that UFM1 could be a biomarker for prognosis and treating OSCC patients.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Humanos , Neoplasias Bucais/metabolismo , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Linhagem Celular Tumoral , Prognóstico , Proliferação de Células , Movimento Celular/genética , Proteínas
9.
World J Urol ; 41(12): 3635-3642, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37819588

RESUMO

PURPOSE: Urinary incontinence is a common complication following robot-assisted radical prostatectomy (RARP). Few studies have explored the relationships and differences between stress urinary incontinence (SUI) and urgent urinary incontinence (UUI) after RARP. This study aimed to investigate the occurrence rates and risk factors of UUI and SUI in short term after RARP. METHODS: We prospectively included prostate cancer patients who underwent RARP by a single surgeon. Demographics, lower urinary tract function, oncology, and follow-ups were recorded. Occurrence rates and risk factors of UUI and SUI within 3 months after catheter withdrawal were calculated. RESULTS: The study cohort included 363 subjects with a mean age of 66.05 years. The median preoperative International Prostate Symptom Score (IPSS) was 14 (range 0-35), and the median Overactive Bladder Symptom Score (OABSS) was 3 (range 0-14). The occurrence rate of UUI and SUI at 3 months after catheter withdrawal was 8.5% (31/363) and 15.2% (55/363). Nearly all patients with UUI also had SUI. Diabetes history and high OABSS before RARP were independent risk factors for UUI, especially within 1 month after catheter withdrawal. The Gleason Score was an independent risk factor for SUI at 3 months after catheter withdrawal. Additionally, UUI but not SUI might be an influencing factor for decision-making regarding postoperative radiotherapy. CONCLUSION: The occurrence rate of SUI after RARP was persistently higher than that of UUI. Nearly all of the patients with UUI simultaneously had SUI. The risk factors of UUI and SUI after RARP were absolutely different.


Assuntos
Neoplasias da Próstata , Procedimentos Cirúrgicos Robóticos , Robótica , Bexiga Urinária Hiperativa , Incontinência Urinária por Estresse , Incontinência Urinária , Masculino , Humanos , Idoso , Próstata , Incontinência Urinária por Estresse/etiologia , Incontinência Urinária por Estresse/complicações , Incontinência Urinária/epidemiologia , Incontinência Urinária/etiologia , Prostatectomia/efeitos adversos , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Bexiga Urinária Hiperativa/complicações , Neoplasias da Próstata/complicações
10.
Wei Sheng Yan Jiu ; 52(5): 702-709, 2023 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-37802892

RESUMO

OBJECTIVE: The effects of nano-carbon black on neural behavior and Th17 cell infiltration in mice were investigated by establishing a mice model of subacute dynamic inhalation of carbon black aerosol. METHODS: 36 SPF grade male C57BL/6 mice were randomly divided into a control group(clean air), a low carbon black group(15 mg/m~3), and a high carbon black group(30 mg/m~3). Nano-carbon black particles were blown into the dynamic exposure cabinet by aerosol generator for 28 days. Morris water maze test and open field test were used to detect the neural behavior of mice. The pathological changes of prefrontal cortex in mice were observed by HE staining. The proportion of Th17/CD4~+ cells in peripheral blood and brain tissue of mice was detected by flow cytometry. Western blotting was used to detect the protein expression of interleukin(IL)-17 and IL-23 in the prefrontal cortex of mice. RESULTS: The result of open field test showed that compared with the control group, the central area residence time and standing times of mice in the low and high carbon black groups decreased significantly(P<0.05), and the defecation times of mice in the high carbon black group increased significantly(P<0.05). The central area residence time of mice in the high carbon black group was significantly lower than that in the low carbon black group(P<0.05). The Morris water maze result showed that the escape latency of the high carbon black group mice on the 3rd day was significantly higher than that of the control group(P<0.05). Meanwhile, the escape latency of the carbon black group mice on the 4th day was significantly higher than that of the control group(P<0.05). The positioning navigation test showed that the number of mice crossing the platform in the high carbon black group was significantly higher than that in the control group(P<0.05). The HE staining result showed that the neural cells in the prefrontal cortex of the control group mice were round, the cytoplasm was plump and evenly distributed, and the nucleus was clearly visible in an oval shape. The low carbon black group showed that the neural cells were deep staining of nerve cells, blurred structure, and nuclear pyknosis. The high carbon black group further intensified. The flow cytometry result showed that compared with the control group, the percentage of Th17/CD4~+T cells in the peripheral blood of the carbon black group mice was significantly increased, and the high carbon black group mice were significantly higher than the low carbon black group(P<0.05). Meanwhile, the percentage of Th17/CD4~+T cells in the brain tissue of carbon black treated mice significantly increased(P<0.05). The high carbon black group was significantly higher than the low carbon black group(P<0.05). Western blotting result showed that compared with the control group, the expression of IL-17 and IL-23 proteins in the prefrontal cortex of the carbon black group mice brain tissue was significantly increased(P<0.05). Compared with the low carbon black group, the expression of IL-17 and IL-23 proteins in the prefrontal cortex of the high carbon black group mice brain tissue was significantly increased(P<0.05). The difference was statistically significant. CONCLUSION: Nano-carbon black exposure can lead to an increase in Th17 cells in peripheral blood and brain tissue of mice, which in turn promotes damage to the prefrontal cortex of mice, and ultimately causes neurobehavioral changes in mice.


Assuntos
Interleucina-17 , Células Th17 , Camundongos , Animais , Masculino , Células Th17/metabolismo , Fuligem/toxicidade , Camundongos Endogâmicos C57BL , Aerossóis , Interleucina-23
11.
Curr Med Sci ; 43(4): 631-646, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37558863

RESUMO

Cancer treatment has evolved rapidly due to major advances in tumor immunity research. However, due to the complexity, heterogeneity, and immunosuppressive microenvironment of tumors, the overall efficacy of immunotherapy is only 20%. In recent years, nanoparticles have attracted more attention in the field of cancer immunotherapy because of their remarkable advantages in biocompatibility, precise targeting, and controlled drug delivery. However, the clinical application of nanomedicine also faces many problems concerning biological safety, and the synergistic mechanism of nano-drugs with immunity remains to be elucidated. Our study summarizes the functional characteristics and regulatory mechanisms of nanoparticles in the cancer immune microenvironment and how nanoparticles activate and long-term stimulate innate immunity and adaptive immunity. Finally, the current problems and future development trends regarding the application of nanoparticles are fully discussed and prospected to promote the transformation and application of nanomedicine used in cancer treatment.


Assuntos
Neoplasias , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Imunoterapia , Nanomedicina , Sistemas de Liberação de Medicamentos , Imunidade Adaptativa , Microambiente Tumoral
12.
Int J Surg ; 109(9): 2742-2750, 2023 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-37335987

RESUMO

BACKGROUND: The application of pelvic organ preserving-radical cystectomy (POPRC) in female patients with bladder cancer has attracted more and more attention in recent years. In the current study, the authors aim to compare the long-term oncological outcomes of POPRC versus standard radical cystectomy (SRC) in a large multicenter retrospective cohort. PATIENTS AND METHODS: Data on female patients with bladder cancer who underwent POPRC or SRC in January 2006 and April 2018 were included from three Chinese urological centers. The primary outcome was overall survival (OS). Secondary outcomes were cancer-specific survival and recurrence-free survival. To decrease the effect of unmeasured confounders associated with treatment selection, 1:1 propensity score matching was performed. RESULTS: Among the 273 enrolled patients, 158 underwent POPRC (57.9%), and 115 underwent SRC (42.1%). The median follow-up time was 38.6 (15.9-62.5) months. After propensity score matching, each cohort included 99 matched patients. The OS ( P =0.940), cancer-specific survival ( P =0.957), and recurrence-free survival ( P =0.476) did not differ significantly from the two matched cohorts. Subgroup analysis confirmed that the OS was similar between the patients treated with POPRC and SRC across all subgroups examined (all P > 0.05). In multivariable analysis, the surgical method (SRC vs. POPRC) was not an independent risk factor for OS (Hazard ratio 0.874, 95% CI 0.592-1.290; P =0.498). CONCLUSIONS: The results showed that no significant difference in long-term survival was determined between female patients undergoing SRC and those undergoing POPRC.


Assuntos
Cistectomia , Neoplasias da Bexiga Urinária , Humanos , Feminino , Cistectomia/métodos , Pontuação de Propensão , Estudos Retrospectivos , Resultado do Tratamento , Neoplasias da Bexiga Urinária/cirurgia
13.
Front Oncol ; 13: 1086517, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37064136

RESUMO

Simple summary: Somatic and germline aberrations in homologous recombinant repair (HHR) genes are associated with increased incidence and poor prognosis for prostate cancer. Through next-generation sequencing of prostate cancer patients across all clinical states from north China, here the authors identified a somatic mutational rate of 3% and a germline mutational rate of 3.9% for HRR genes using 200 tumor tissues and 714 blood specimens. Thus, mutational rates in HRR genes were lower compared with previous studies. Background: Homologous recombination repair deficiency is associated with higher risk and poorer prognosis for prostate cancer. However, the landscapes of somatic and germline mutations in these genes remain poorly defined in Chinese patients, especially for those with localized disease and those from north part of China. In this study, we explore the genomic profiles of these patients. Methods: We performed next-generation sequencing with 200 tumor tissues and 714 blood samples from prostate cancer patients at Peking University First Hospital, using a 32 gene panel including 19 homologous recombination repair genes. Results: TP53, PTEN, KRAS were the most common somatic aberrations; BRCA2, NBN, ATM were the most common germline aberrations. In terms of HRR genes, 3% (6/200) patients harbored somatic aberrations, and 3.8% (28/714) patients harbored germline aberrations. 98.0% (196/200) somatic-tested and 72.7% (519/714) germline tested patients underwent prostatectomy, of which 28.6% and 42.0% had Gleason scores ≥8 respectively. Gleason scores at either biopsy or prostatectomy were predictive for somatic aberrations in general and in TP53; while age of onset <60 years old, PSA at diagnosis, and Gleason scores at biopsy were clinical factors associated with positive germline aberrations in BRCA2/ATM. Conclusions: Our results showed a distinct genomic profile in homologous recombination repair genes for patients with prostate cancer across all clinical states from north China. Clinicians may consider to expand the prostate cancer patients receiving genetic tests to include more individuals due to the weak guiding role by the clinical factors currently available.

14.
Eur J Pharm Biopharm ; 187: 12-23, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37031731

RESUMO

Gallic acid (GA) is a naturally occurring polyphenolic compound exhibiting anti-tumor activity. To clarify the capability of GA in optimizing the in vitro/in vivo properties of the first line anti-tumor drug 5-fluorouracil (5-FU) and achieve synergistically enhanced anti-tumor activity, a novel cocrystal hydrate of 5-FU-GA-H2O was successfully screened and characterized based on various spectroscopic and experimental analysis including Fourier transform infrared spectroscopy (FT-IR), Raman spectra (Raman), powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), thermogravimetric (TG) and scanning electric microscope (SEM) techniques. The results suggested the existence of hydrogen bonding interactions between C=O group of 5-FU and O-H group of GA. Although the dissolution rate and solubility of 5-FU-GA-H2O cocrystal were slowed and lowered compared with that of 5-FU, respectively, the membrane permeability was enhanced for cocrystal compared with that of intact 5-FU and physical mixture (PM) of 5-FU and GA. For the cocrystal, the cumulative amount per unit area of permeated 5-FU in the first 10 h was 2.56 and 9.97 times of that of pure 5-FU and PM, respectively, in the case that transmembrane behavior of 5-FU depended on the type of solution from which the powder was dissolved. Meanwhile, improvement on oral bioavailability by co-crystallization was observed; AUC0-t of cocrystal was 2.78-fold higher than that of 5-FU. Furthermore, the cocrystal displayed a superior cytotoxic activity on 4T1 mouse breast cancer cells compared with pure 5-FU and even the PM. It was confirmed that the cocrystal solution induced higher autophagic flux than those of 5-FU and PM in 4T1 cell, suggesting that autophagy rather than apoptosis mainly mediated cell death. The obvious difference of tumor inhibition activity between PM and cocrystal in intraperitoneal injection administration indicated that some of the interactions formed in the solid cocrystal could retain in solution in some way. Benefiting from synergistic cytotoxicity, drug efficacy in vivo was enhanced through injection administration of solution from which cocrystal was dissolved.


Assuntos
Antineoplásicos , Neoplasias , Camundongos , Animais , Fluoruracila/farmacologia , Fluoruracila/química , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Injeções Intraperitoneais , Pós , Antineoplásicos/farmacologia , Difração de Raios X , Solubilidade , Varredura Diferencial de Calorimetria
15.
J Surg Case Rep ; 2023(3): rjad159, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37016702

RESUMO

Inflammatory breast cancer (IBC) is a rare but aggressive form of breast cancer, accounting for 0.5-2% of all diagnoses of invasive breast cancers. Yet, it is associated with very poor prognosis and outcomes, with documented 2- and 5-year survival rates around 84% and 40%, respectively, as compared to 90.6% of all breast cancers. Breast auto-amputation is also a rare complication of locally advanced breast cancer, associated with distressing symptoms for these patients. In this study, we report a 67-year-old female with a delayed diagnosis of IBC with a rare sequela of auto-amputation of the affected breast. The delay in diagnosis of >6 months led to a delay in the necessary treatment. She received neoadjuvant chemoradiotherapy and underwent a palliative right salvage mastectomy with level 2 axillary dissection.

16.
ACS Nano ; 17(11): 10407-10422, 2023 06 13.
Artigo em Inglês | MEDLINE | ID: mdl-37120837

RESUMO

Since glioblastomas (GBMs) are radioresistant malignancies and most GBM recurrences occur in radiotherapy, increasing the effectiveness of radiotherapy by gene-silencing has recently attracted attention. However, the difficulty in precisely tuning the composition and RNA loading in nanoparticles leads to batch-to-batch variations of the RNA therapeutics, thus significantly restricting their clinical translation. Here, we bioengineer bacteriophage Qß particles with a designed broccoli light-up three-way junction (b-3WJ) RNA scaffold (contains two siRNA/miRNA sequences and one light-up aptamer) packaging for the silencing of genes in radioresistant GBM cells. The in vitro results demonstrate that the cleavage of de novo designed b-3WJ RNA by Dicer enzyme can be easily monitored in real-time using fluorescence microscopy, and the TrQß@b-3WJLet-7gsiEGFR successfully knocks down EGFR and IKKα simultaneously and thereby inactivates NF-κB signaling to inhibit DNA repair. Delivery of TrQß@b-3WJLet-7gsiEGFR through convection-enhanced delivery (CED) infusion followed by 2Gy X-ray irradiation demonstrated that the median survival was prolonged to over 60 days compared with the 2Gy X-ray irradiated group (median survival: 31 days). Altogether, the results of this study could be critical for the design of RNAi-based genetic therapeutics, and CED infusion serves as a powerful delivery system for promoting radiotherapy against GBMs without evidence of systemic toxicity.


Assuntos
Bacteriófagos , Glioblastoma , MicroRNAs , Nanopartículas , Humanos , Glioblastoma/genética , Glioblastoma/terapia , Glioblastoma/patologia , Terapêutica com RNAi/métodos , Linhagem Celular Tumoral , MicroRNAs/genética , RNA Interferente Pequeno/genética , Interferência de RNA
17.
Int J Surg ; 109(6): 1668-1676, 2023 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-37076132

RESUMO

BACKGROUND: The best follow-up strategy for cancer survivors after treatment should balance the effectiveness and cost of disease detection while detecting recurrence as early as possible. Due to the low incidence of gastric neuroendocrine carcinoma and mixed adenoneuroendocrine carcinoma [G-(MA)NEC], high-level evidence-based follow-up strategies is limited. Currently, there is a lack of consensus among clinical practice guidelines regarding the appropriate follow-up strategies for patients with resectable G-(MA)NEC. MATERIALS AND METHODS: The study included patients diagnosed with G-(MA)NEC from 21 centers in China. The random forest survival model simulated the monthly probability of recurrence to establish an optimal surveillance schedule maximizing the power of detecting recurrence at each follow-up. The power and cost-effectiveness were compared with the National Comprehensive Cancer Network, European Neuroendocrine Tumor Society, and European Society for Medical Oncology Guidelines. RESULTS: A total of 801 patients with G-(MA)NEC were included. The patients were stratified into four distinct risk groups utilizing the modified TNM staging system. The study cohort comprised 106 (13.2%), 120 (15.0%), 379 (47.3%), and 196 cases (24.5%) for modified groups IIA, IIB, IIIA, and IIIB, respectively. Based on the monthly probability of disease recurrence, the authors established four distinct follow-up strategies for each risk group. The total number of follow-ups 5 years after surgery in the four groups was 12, 12, 13, and 13 times, respectively. The risk-based follow-up strategies demonstrated improved detection efficiency compared to existing clinical guidelines. Further Markov decision-analytic models verified that the risk-based follow-up strategies were better and more cost-effective than the control strategy recommended by the guidelines. CONCLUSIONS: This study developed four different monitoring strategies based on individualized risks for patients with G-(MA)NEC, which may improve the detection power at each visit and were more economical, effective. Even though our results are limited by the biases related to the retrospective study design, we believe that, in the absence of a randomized clinical trial, our findings should be considered when recommending follow-up strategies for G-(MA)NEC.


Assuntos
Sobreviventes de Câncer , Carcinoma Neuroendócrino , Neoplasias Gástricas , Humanos , Estudos Retrospectivos , Estudos de Coortes , Recidiva Local de Neoplasia , Carcinoma Neuroendócrino/cirurgia , Carcinoma Neuroendócrino/patologia
18.
Front Endocrinol (Lausanne) ; 14: 1118564, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36967766

RESUMO

Objective: To evaluate the quality of surgical guidelines on bariatric/metabolic surgery. Methods: Four independent reviewers used the AGREE II (The Appraisal of Guidelines for Research and Evaluation II) tool to assess the methodological quality of the included guidelines and conducted a comparative analysis of the main recommendations for surgical methods of these guidelines. Results: Nine surgical guidelines were included in this study. Five articles with AGREE II scores over 60% are worthy of clinical recommendation. The field of rigor of development was relatively low, with an average score of 50.82%. Among 15 key recommendations and the corresponding best evidence in the guidelines, only 4 key recommendations were grade A recommendations. Conclusions: The quality of metabolic and bariatric guidelines is uneven, and there is much room for improvement.


Assuntos
Cirurgia Bariátrica , Guias de Prática Clínica como Assunto , Cirurgia Bariátrica/normas , Guias de Prática Clínica como Assunto/normas
19.
J Endourol ; 37(5): 568-574, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36924278

RESUMO

Objective: To compare the efficacy and safety of robot-assisted laparoscopic radical prostatectomy (RARP) performed using the KangDuo surgical robot system to the da Vinci Si robotic system in clinically localized prostate cancer (KD-RARP vs DV-RARP). Methods: A total of 16 patients underwent extraperitoneal KD-RARP performed by a single experienced surgeon using the KangDuo surgical robot system between May 2021 and August 2021. The data were prospectively collected. The most recent 16 cases of extraperitoneal DV-RARP performed in 2021 by the same surgeon were selected from a prospectively maintained database for comparison to prevent operator variability. Preoperative, perioperative, and postoperative data were collected and compared between the two groups. Results: No significant difference was noted between the two groups in terms of basic clinical characteristics. All operations were performed successfully without open or traditional laparoscopic conversion. KD-RARP had a significantly longer operation time compared with DV-RARP (127 [107-159] vs 70.5 [54-90] minutes, p < 0.001). No significant differences between the two groups were observed in neurovascular bundle sparing, estimated blood loss, postoperative hospital stay duration, complications, positive surgical margins, biochemical recurrence, and continence recovery 3 months after catheter removal. Conclusions: RARP using the KangDuo surgical robot system achieved similar short-term oncological and functional outcomes with a disadvantage in operation time compared with the da Vinci Si robotic system. A multicenter randomized clinical trial with a larger sample size is needed for more experience.


Assuntos
Laparoscopia , Neoplasias da Próstata , Procedimentos Cirúrgicos Robóticos , Robótica , Masculino , Humanos , Próstata/cirurgia , Prostatectomia , Neoplasias da Próstata/cirurgia , Resultado do Tratamento
20.
World J Urol ; 41(2): 501-508, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36581769

RESUMO

PURPOSE: To compare the perioperative and oncologic outcomes between minimally invasive pelvic organ-preserving radical cystectomy (MIPOPRC) and open pelvic organ-preserving radical cystectomy (open POPRC) among female patients with bladder cancer (BCa). METHODS: We identified female patients who underwent POPRC for BCa at three centers between January 2006 and April 2018. Female patients who underwent open POPRC were matched with those who underwent MIPOPRC using 1:1 propensity score (PS) matching. The patient demographics and perioperative and oncologic outcomes were evaluated for the comparison between MIPOPRC and open POPRC. RESULTS: Among the 158 patients enrolled, 83 patients underwent MIPOPRC, and 75 underwent open POPRC. A total of 60 MIPOPRC and 60 open POPRC patients were matched successfully. The cancer-specific survival (CSS) and recurrence-free survival (RFS) did not differ significantly in the propensity score-weighted cohort (p = 0.297 and p = 0.600, respectively). Subgroup analysis by age and pathologic stage in the matched cohort revealed that CSS and RFS were with no differences among all subgroups. Moreover, multivariable Cox regression analyses showed that the surgical approach (MIPOPRC vs open POPRC) was not a predictor of CSS (p = 0.250). CONCLUSION: MIPOPRC was non-inferior to open POPRC in terms of oncologic outcomes among female patients. MIPOPRC could be technically feasible in selected female patients with BCa.


Assuntos
Cistectomia , Neoplasias da Bexiga Urinária , Humanos , Feminino , Cistectomia/efeitos adversos , Pontuação de Propensão , Resultado do Tratamento , Bexiga Urinária/cirurgia , Neoplasias da Bexiga Urinária/patologia
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