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Developing nature-inspired nanomaterials with enzymatic activity is essential in combating bacterial biofilms. Here, it is reported that incorporating the carboxylic acid in phenolic/Fe nano-networks can efficiently manipulate their peroxidase-like activity via the acidic microenvironment and neighboring effect of the carboxyl group. The optimal gallic acid/Fe (GA/Fe) nano-networks demonstrate highly enzymatic activity in catalyzing H2 O2 into oxidative radicals, damaging the cell membrane and extracellular DNA in Streptococcus mutans biofilms. Theoretical calculation suggests that the neighboring carboxyl group can aid the H2 O2 adsorption, free radical generation, and catalyst reactivation, resulting in superb catalytic efficiency. Further all-atom simulation suggests the peroxidation of lipids can increase the cell membrane fluidity and permeability. Also, GA/Fe nano-networks show great potential in inhibiting tooth decay and treating other biofilm-associated diseases without affecting the commensal oral flora. This strategy provides a facile and scale-up way to prepare the enzyme-like materials and manipulate their enzymatic activity for biomedical applications.
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Peroxidase , Streptococcus mutans , Peroxidase/metabolismo , Streptococcus mutans/genética , Streptococcus mutans/metabolismo , BiofilmesRESUMO
Recently, the emergence of immunotherapy has revolutionized traditional tumour treatment. However, effective treatments for patients exhibiting αPD-1 resistance are still lacking. In our study, a combination of cytosine-phosphate-guanine oligodeoxynucleotides (CpG-ODNs), anti-OX40 and cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) injection in situ systematically generated a robust antitumour immune response in TC1 and B16 cells, which are αPD-1-resistant malignancies. More precisely, this method activates both adaptive and innate immunity. Additionally, in situ vaccination with CpG/αOX40/cGAMP fully activates the production of cytokines. However, the combination of αPD-1 does not improve the efficacy of triple therapy, prompting further questions. Collectively, the combination of CpG/αOX40/cGAMP causes the regression of various αPD-1-resistant tumours through the full mobilization of innate and adaptive immunity. In addition, we explored the therapeutic effect of triple therapy on the αPD-1-sensitive cell line CT26. The results showed that triple therapy could significantly enhance the therapeutic effect of αPD-1, and some mice even achieved complete tumour regression after the combined application of αPD-1 and triple treatment.
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Neoplasias , Nucleotídeos Cíclicos , Animais , Humanos , Imunidade Inata , Imunoterapia , Camundongos , Nucleotídeos Cíclicos/farmacologiaRESUMO
BACKGROUND: There are limited data from retrospective studies regarding whether survival outcomes after laparoscopic or robot-assisted radical hysterectomy (minimally invasive surgery) are equivalent to those after open abdominal radical hysterectomy (open surgery) among women with early-stage cervical cancer. METHODS: In this trial involving patients with stage IA1 (lymphovascular invasion), IA2, or IB1 cervical cancer and a histologic subtype of squamous-cell carcinoma, adenocarcinoma, or adenosquamous carcinoma, we randomly assigned patients to undergo minimally invasive surgery or open surgery. The primary outcome was the rate of disease-free survival at 4.5 years, with noninferiority claimed if the lower boundary of the two-sided 95% confidence interval of the between-group difference (minimally invasive surgery minus open surgery) was greater than -7.2 percentage points (i.e., closer to zero). RESULTS: A total of 319 patients were assigned to minimally invasive surgery and 312 to open surgery. Of the patients who were assigned to and underwent minimally invasive surgery, 84.4% underwent laparoscopy and 15.6% robot-assisted surgery. Overall, the mean age of the patients was 46.0 years. Most patients (91.9%) had stage IB1 disease. The two groups were similar with respect to histologic subtypes, the rate of lymphovascular invasion, rates of parametrial and lymph-node involvement, tumor size, tumor grade, and the rate of use of adjuvant therapy. The rate of disease-free survival at 4.5 years was 86.0% with minimally invasive surgery and 96.5% with open surgery, a difference of -10.6 percentage points (95% confidence interval [CI], -16.4 to -4.7). Minimally invasive surgery was associated with a lower rate of disease-free survival than open surgery (3-year rate, 91.2% vs. 97.1%; hazard ratio for disease recurrence or death from cervical cancer, 3.74; 95% CI, 1.63 to 8.58), a difference that remained after adjustment for age, body-mass index, stage of disease, lymphovascular invasion, and lymph-node involvement; minimally invasive surgery was also associated with a lower rate of overall survival (3-year rate, 93.8% vs. 99.0%; hazard ratio for death from any cause, 6.00; 95% CI, 1.77 to 20.30). CONCLUSIONS: In this trial, minimally invasive radical hysterectomy was associated with lower rates of disease-free survival and overall survival than open abdominal radical hysterectomy among women with early-stage cervical cancer. (Funded by the University of Texas M.D. Anderson Cancer Center and Medtronic; LACC ClinicalTrials.gov number, NCT00614211 .).
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Histerectomia/métodos , Procedimentos Cirúrgicos Minimamente Invasivos , Neoplasias do Colo do Útero/cirurgia , Adenocarcinoma/mortalidade , Adenocarcinoma/cirurgia , Adulto , Carcinoma Adenoescamoso/mortalidade , Carcinoma Adenoescamoso/cirurgia , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/cirurgia , Intervalo Livre de Doença , Feminino , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Estudos Prospectivos , Taxa de Sobrevida , Neoplasias do Colo do Útero/mortalidade , Neoplasias do Colo do Útero/patologiaRESUMO
OBJECTIVE: Lipids have been evaluated for their possible role in cancer survival prediction. The aim of the current study was to investigate the prognostic value of lipids on overall survival for stage IB1-IIA2 cervical cancer patients. METHODS: A retrospective study including cervical cancer patients with early-stage (FIGO 2009 stage IB1-IIA2) disease was conducted from January 2012 to February 2017. Patients with any history of liver disease or other cancers, and patients who took any medications known to influence lipid metabolism, were excluded. We measured various factors in patients' lipid profiles including total cholesterol, triglycerides, high-density lipoprotein, and low-density lipoprotein, and assessed these four parameters together with clinicopathological features to identify the significant prognostic factors for overall survival. RESULTS: A total of 583 patients with median age 53 (range 25-82) years were included. Among them, 283 (48.5%) patients were in FIGO stage IB1, 44 patients (7.6%) in stage IB2, 189 (32.4%) patients in stage IIA1, and the remaining 67 (11.5%) patients were in stage IIA2. Using univariable Cox proportional hazard analysis and subsequent multivariable analysis, total cholesterol, triglycerides, and pelvic lymph node status were shown to be independent prognostic factors for overall survival (p<0.05 for all). Furthermore, the results of the Kaplan-Meier survival curves showed that both the high total cholesterol group and the high triglycerides group were associated with worse overall survival (p=0.002 and p=0.001, respectively) CONCLUSIONS: Our study showed that total triglycerides and total cholesterol may serve as potential predictors for overall survival in patients with cervical cancer. Cervical cancer patients may benefit from treatments after adjusting their triglycerides and total cholesterol levels.
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Hipercolesterolemia/sangue , Triglicerídeos/sangue , Neoplasias do Colo do Útero/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/sangue , Feminino , Humanos , Hipercolesterolemia/tratamento farmacológico , Estimativa de Kaplan-Meier , Lipoproteínas HDL/sangue , Lipoproteínas LDL/sangue , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Período Pré-Operatório , Estudos Retrospectivos , Neoplasias do Colo do Útero/mortalidadeRESUMO
BACKGROUND: Villoglandular adenocarcinoma is a rare sub-type of cervical adenocarcinoma. OBJECTIVE: To analyze the clinicopathological features and evaluate the prognosis of patients with villoglandular adenocarcinoma of the cervix. METHODS: Patient characteristics, procedure, pathology, and surgical outcomes were retrospectively reviewed in patients with villoglandular adenocarcinoma between November 2006 and June 2019 from multiple centers in China. In order to explore the difference between villoglandular adenocarcinoma and routine adenocarcinoma, patients (FIGO 2009 stage IA1-IB2) who had complete data during the same time period were included. RESULTS: A total of 60 patients with villoglandular adenocarcinoma and 104 with standard adenocarcinoma were included. The median age of the patients with villoglandular adenocarcinoma was 42 years (range 27-68). The most common 2009 FIGO stage was IB1 in 39 (65%) patients with villoglandular adenocarcinoma. A total of 23 patients underwent laparoscopic surgery (two total hysterectomies, 21 radical hysterectomies) and the other 37 patients underwent laparotomy (three total hysterectomies, 34 radical hysterectomies). A total of 56 patients underwent lymphadenectomy and three (5.4%) had positive lymph nodes. Fifteen (25%) patients had one or both ovaries preserved. Seven patients were lost to follow-up. The median follow-up time for the entire group was 50.2 months (range 5.1-154.6). No deaths or recurrences occurred. Excluding six patients with FIGO 2009 stage II, the 5-year disease-free survival of the 47 patients with villoglandular adenocarcinoma with FIGO 2009 stage I for whom there was follow-up, was significantly higher than that of the 104 patients with standard cervical adenocarcinoma (100% vs 92.2%, log-rank p=0.039). However, the 5-year overall survival of the two groups did not differ (100% vs 95.7%, log-rank p=0.11). CONCLUSION: Villoglandular adenocarcinoma has a favorable prognosis. Further studies are needed to provide more details of treatment strategies and prognosis.
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Adenocarcinoma/diagnóstico , Neoplasias do Colo do Útero/diagnóstico , Adenocarcinoma/patologia , Adulto , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Prognóstico , Neoplasias do Colo do Útero/patologiaRESUMO
BACKGROUND: The prolapse of a ruptured and extruded bladder after vaginal hysterectomy is rare in clinical practice. We report the case of a significant mass that prolapsed from the vagina after a vaginal hysterectomy in a multiparous postmenopausal woman. CASE PRESENTATION: A 67-year old multiparous postmenopausal Chinese woman was found to have a significant mass extruding from the vagina after a vaginal hysterectomy. The mass was a ruptured and everted bladder, and the diagnosis was confirmed after physical and imaging examinations and urethral catheterization. The patient underwent an emergency operation for mass reduction, bladder repair, and partial colpocleisis under general anesthesia. She recovered without prolapse or urinary drainage complications after 35 months of follow-up. CONCLUSIONS: The present case serves as a guide for the management of patients with pelvic organ prolapse. The condition of patients should be carefully evaluated before surgery, and individualized operation should be performed. Careful postoperative follow-up is crucial for the timely exclusion of complications, especially in elderly patients with persistently increased abdominal pressure.
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Cistostomia , Histerectomia Vaginal/efeitos adversos , Prolapso de Órgão Pélvico/cirurgia , Bexiga Urinária/cirurgia , Incontinência Urinária/etiologia , Idoso , Feminino , Humanos , Pós-Menopausa , Resultado do Tratamento , Bexiga Urinária/diagnóstico por imagem , Cateterismo Urinário , Procedimentos Cirúrgicos Urológicos , Vagina/cirurgiaRESUMO
BACKGROUND: Cervical cancer (CC) is one of the most common gynaecological cancers. The gene signature is believed to be reliable for predicting cancer patient survival. However, there is no relevant study on the relationship between the glycolysis-related gene (GRG) signature and overall survival (OS) of patients with CC. METHODS: We extracted the mRNA expression profiles of 306 tumour and 13 normal tissues from the University of California Santa Cruz (UCSC) Database. Then, we screened out differentially expressed glycolysis-related genes (DEGRGs) among these mRNAs. All patients were randomly divided into training cohort and validation cohort according to the ratio of 7: 3. Next, univariate and multivariate Cox regression analyses were carried out to select the GRG with predictive ability for the prognosis of the training cohort. Additionally, risk score model was constructed and validated it in the validation cohort. RESULTS: Six mRNAs were obtained that were associated with patient survival. The filtered mRNAs were classified into the protective type (GOT1) and the risk type (HSPA5, ANGPTL4, PFKM, IER3 and PFKFB4). Additionally, by constructing the prognostic risk score model, we found that the OS of the high-risk group was notably poorer, which showed good predictive ability both in training cohort and validation cohort. And the six-gene signature is a prognostic indicator independent of clinicopathological features. Through the verification of PCR, the results showed that compared with the normal cervial tissuses, the expression level of six mRNAs were significantly higher in the CC tissue, which was consistent with our findings. CONCLUSIONS: We constructed a glycolysis-related six-gene signature to predict the prognosis of patients with CC using bioinformatics methods. We provide a thorough comprehension of the effect of glycolysis in patients with CC and provide new targets and ideas for individualized treatment.
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Glicólise/genética , Neoplasias do Colo do Útero/genética , Chaperona BiP do Retículo Endoplasmático , Feminino , Humanos , Pessoa de Meia-Idade , Prognóstico , Análise de Sobrevida , Neoplasias do Colo do Útero/mortalidadeRESUMO
OBJECTIVE: There is recent evidence that demonstrates worse oncologic outcomes associated with minimally invasive radical hysterectomy when compared with open radical hysterectomy, particularly in patients with tumors >2 cm. The aim of our study was to retrospectively evaluate the oncological outcomes between laparoscopic and open radical hysterectomy in International Federation of Gynecology and Obstetrics(FIGO) 2009 stage IB1 (FIGO 2009) cervical cancer patients with tumor size ≤2 cm. METHODS: A retrospective review of medical records was performed to identify patients who underwent either laparoscopic or open radical hysterectomy during January 2010 and December 2018. Inclusion criteria were: (1) histologically confirmed cervical cancer including all histological types; (2) FIGO 2009 stage IB1; (3) tumor size ≤2 cm (determined by pelvic examination, magnetic resonance imaging or transvaginal ultrasound); (4) had undergone radical hysterectomy (type II or III) with pelvic and/or para-aortic lymphadenectomy as primary surgical treatment; (5) had follow-up information. Patients with FIGO 2009 stage IA1 or IA2, tumor size >2 cm, or who received neo-adjuvant chemotherapy before surgery, those with cervical cancer incidentally found after simple hysterectomy, or with insufficient data were excluded. Concurrent comparison between the laparoscopic and open cohorts was made for disease-free survival and overall survival. RESULTS: A total of 325 cervical cancer patients were included; of these, 129 patients underwent laparoscopic surgery and 196 patients had open surgery. The median follow-up times were 51.8 months (range 2-115) for laparoscopic surgery and 49.5 months (range 3-108) for open surgery. Patients in the laparoscopic group had significantly worse 5 year disease-free survival than those in the open group (90.4% vs 97.7%; p=0.02). There was no significant difference in 5 year overall survival between groups (96.9% vs 99.4%, p=0.33). The Cox proportional hazards regression analysis indicated that laparoscopic surgery was associated with lower disease-free survival compared with open surgery (adjusted hazard ratio 4.64, 95% CI 1.26 to 17.06; p=0.02). In patients with non-squamous cell carcinoma or with grade II-III, laparoscopic surgery had a significantly worse 5 year disease-free survival compared with the open surgery group (74% vs 100%, p=0.01, and 88.8% vs 98.0%, p=0.02, respectively). CONCLUSION: Laparoscopic radical hysterectomy was associated with worse disease-free survival for stage IB1 (FIGO 2009) cervical cancer patients with tumor size ≤2 cm compared with open radical hysterectomy. Further studies may shed additional light on the impact of minimally invasive surgery in this low-risk patient population.
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Neoplasias do Colo do Útero/cirurgia , Intervalo Livre de Doença , Feminino , Humanos , Histerectomia/métodos , Laparoscopia/métodos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento , Neoplasias do Colo do Útero/patologiaRESUMO
PURPOSE: The objective of this meta-analysis is to investigate and compare the pregnancy outcomes of laparoscopy and open surgery in the treatment of ovarian tumors during pregnancy. METHODS: Search was conducted using MEDLINE, EMBASE, and Cochrane Databases from January 1990 to November 2018. A broad search strategy was used to identify studies comparing laparoscopy and open surgery in pregnancy. Inclusion criteria included comparative studies with the quantitative outcome data on gravida. Two authors independently reviewed and assessed for the quality of included studies according to the Newcastle-Ottawa Scale. Data were extracted for fetal loss, preterm delivery, duration of surgery, blood loss and length of hospital stay. RESULTS: Nine retrospective trials were identified involving 985 patients. No statistical significance was found in fetal loss between laparoscopy and open surgery (P value = 0.334). The pooled estimate for preterm labor statistically significantly decreased for laparoscopy group (P value = 0.014). Reduced operative blood loss was found in laparoscopy group by 83.81 ml (P value = 0.015). Duration of operation may be longer in the laparoscopy group, but without statistical significance (P value = 0.346). Length of hospital stay was shorter in the laparoscopy group with reduction of 1.95 days (P value < 0.001). CONCLUSIONS: The available low-grade evidence suggests that laparoscopic surgery might be a feasible alternative for pregnant women with adnexal masses.
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The article listed above was initially published.
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OBJECTIVE: Ovarian cancer is one of the most lethal of women cancers and lack potent therapeutic options. There have many evidences demonstrate the Notch signaling has deregulation in variety of human malignancies.MK-0752 is a novel potent γ-secretase inhibitor and now assessed in clinical trial for treatment of several types of cancer, our objective was to investigate the anticancer effects and mechanisms of MK-0752 alone or combined with cisplatin in ovarian cancer. METHODS: Cell lines used: A2780, OVCAR3, SKOV3, HO8910PM, the effects of MK-0752 and cisplatin on cell proliferation were measured by MTT assay. The effect of combination treatment was examined by isobologram analysis. The distribution of cell cycle and cell apoptosis were analyzed using PI and Annexin V-FITC/PI staining by flow cytometric analysis. The mechanism in biochemistry was analyzed by using Western blot. Mouse xenograft model of A2780 was established to observe the anti-ovarian cancer effects in vivo setting, nude mice were randomized into four groups (n=6 per group) and treated every 4 days with control (solvent) group, MK-0752(25mg/kg) group, cisplatin (2mg/kg)group, combination group (both of MK-0752 and cisplatin). RESULTS: MK-0752 alone actively induced cell growth inhibition, G2/M phase cell cycle arrest and apoptosis with down-regulation of Notch1 and its downstream effectors including Hes1, XIAP, c-Myc and MDM2 in a dose- and time-dependent manner. Moreover, sequential combination of cisplatin prior to MK-0752 significantly promoted cell apoptosis and inhibited the subcutaneous xenograft growth of ovarian cancer in nude mice. CONCLUSION: Our data supports the sequential combination of cisplatin prior to MK-0752 is a highly promising novel experimental therapeutic strategy against ovarian cancer.
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Secretases da Proteína Precursora do Amiloide/antagonistas & inibidores , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Derivados de Benzeno/uso terapêutico , Neoplasias Ovarianas/tratamento farmacológico , Propionatos/uso terapêutico , Sulfonas/uso terapêutico , Animais , Apoptose/efeitos dos fármacos , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Derivados de Benzeno/administração & dosagem , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Cisplatino/administração & dosagem , Relação Dose-Resposta a Droga , Regulação para Baixo/efeitos dos fármacos , Sinergismo Farmacológico , Feminino , Proteínas de Homeodomínio/metabolismo , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Propionatos/administração & dosagem , Proteínas Proto-Oncogênicas c-mdm2/metabolismo , Proteínas Proto-Oncogênicas c-myc/metabolismo , Receptor Notch1/metabolismo , Sulfonas/administração & dosagem , Fatores de Transcrição HES-1 , Proteínas Inibidoras de Apoptose Ligadas ao Cromossomo X/metabolismoRESUMO
A novel OLED (organic light emitting diode) lighting panel, which uses a special layout design, can reduce the photolithography cycles and process costs and is more reliable. It only needs two steps of photolithography cycles, which include an ITO (InSnO compound transparent oxide) pattern and insulator pattern. There is no need for the metal bus pattern of the ordinary design. The OLED device structure is a type of red-green-blue (RGB)-stacked emitting layer that has a good color index and greater adjustability, which improves the performance of the device. This novel design has the same equipment and material requirement compared to the ordinary design, and it is very beneficial in terms of high volume and low-cost production. It uses a hyper driving method because the entire OLED lighting panel is divided into many sub-emitting units; if one of the sub-emitting units is burned out, it has no effect on the adjacent sub-emitting unit, so the reliability is markedly better than the ordinary design.
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Iluminação , Compostos Orgânicos/química , Semicondutores , Desenho de EquipamentoRESUMO
AIM: This study aimed to investigate the impact of lymph node dissection on the prognosis of early epithelial ovarian cancer and to assess the factors associated with lymph node metastasis. METHODS: In this retrospective study, we collected and analyzed the demographic characteristics, clinical pathological data, and perioperative adverse events in newly diagnosed early epithelial ovarian cancer (EOC) patients, Federation International of Gynecology and Obstetrics (FIGO) stage IA-IIA. The patients underwent surgical treatment at the First, Second, and Third Affiliated Hospitals of Wenzhou Medical University in Zhejiang Province, China, between June 2012 and June 2022. The survival analysis was performed. RESULTS: We enrolled 284 patients in this study, including 246 stage I, 28 stage II, and 10 stage III patients after surgery. Among them, 42 patients did not undergo lymph node dissection, 113 underwent pelvic lymph node dissection only, and 129 underwent pelvic plus para-aortic lymph node dissection. Among the lymph node dissection group, only 8 patients had lymph node metastasis (8/242, 3.3%), including 6 with pelvic lymph node metastasis and 2 with pelvic plus para-aortic lymph node metastasis. The median follow-up duration was 63 months. The systematic lymph node dissection group significantly prolonged the median operation duration and increased intraoperative blood loss and postoperative complications (p < 0.05). Postoperative multivariate Cox regression analysis revealed FIGO stage III as an independent risk factor for Progression-Free-Survival (PFS) and Overall Survival (OS) (p < 0.05). Furthermore, the preoperative cancer antigen 125 (CA125) level was observed as an independent factor affecting lymph node metastasis. CONCLUSIONS: Systematic lymph node dissection showed minimal effect on the survival rate of patients with clinically apparent early epithelial ovarian cancer and increased the postoperative complications of patients.
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Carcinoma Epitelial do Ovário , Excisão de Linfonodo , Metástase Linfática , Neoplasias Ovarianas , Humanos , Feminino , Estudos Retrospectivos , Neoplasias Ovarianas/cirurgia , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/mortalidade , Pessoa de Meia-Idade , Carcinoma Epitelial do Ovário/cirurgia , Carcinoma Epitelial do Ovário/mortalidade , Carcinoma Epitelial do Ovário/patologia , Adulto , Idoso , Estadiamento de Neoplasias , Prognóstico , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Perda Sanguínea Cirúrgica/estatística & dados numéricosRESUMO
Background: We aimed to compare the anesthesia induction effects of oxycodone and sufentanil on postoperative pain in patients undergoing laparoscopic gallbladder-preserving cholecystolithotomy, as well as changes in serum levels of inflammatory factors (TNF-α, IL-6, and IL-10) in the perioperative period. Methods: Sixty patients who underwent laparoscopic gallbladder-preserving cholecystolithotomy were evenly divided into oxycodone (O) and sufentanil (S) groups. In groups O and S, oxycodone (0.3â mg/kg) and sufentanil (0.3â ug/kg) were administered, respectively, followed by propofol (2â mg/kg) and rocuronium (0.6â mg/kg). In both groups, the intraoperative electroencephalography double-frequency index was used to guide the use of sedative and analgesic drugs, assessing the follow-up analgesic effect (VAS), degree of sedation (Ramsey), and postoperative complications at seven different time points (0, 0.5, 2, 4, 6, 8, and 24â h postoperatively). Results: Compared with the S group, patients in the O group exhibited lower VAS scores within 24â h postoperatively (P < 0.001), but there was no statistical difference between wound and shoulder pain scores (P > 0.05). Regarding postoperative awakening and extubation duration, O group patients experienced shorter times and better remedial analgesia (P < 0.05). In terms of the degree of sedation, the Ramsay score decreased at 0â h postoperatively compared with the S group (P < 0.001). Conclusion: Compared with sufentanil, oxycodone anesthesia induced better postoperative analgesia and less inflammatory responses in patients undergoing laparoscopic gallbladder-preserving cholecystolithotomy. Clinical Trial Registration: This study has been approved by the Ethics Committee of Peking University Shougang Hospital, with ethical approval (No. IRBK-2020-009), and has completed registration in the Chinese Clinical Trials Register (http://www.chictr.org.cn/) (ChiCTR2000031230).
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Ovarian cancer (OC) ranks among the prevalent tumors affecting the female reproductive system. The aim of this study was to evaluate mitochondria-associated platinum resistance genes using organoid models. Univariate Cox regression, LASSO and multivariate Cox regression analyses were performed on The Cancer Genome Atlas (TCGA) database to construct 2-gene prognostic signature (MUL1 and SSBP1), and GSE26712 dataset was used for external validation. In addition, the relationship between MUL1 and platinum resistance was examined by organoid culture, lentiviral transduction, CCK8 assay, and Western blot. The results showed that patients in the high-risk group exhibited significantly worse OS (P = 0.002, P = 0.017). Drug sensitivity analysis revealed that platinum resistance increased with the upregulation of MUL1 expression (Cor = 0.5154, P = 0.02). Our experimental findings demonstrated that knockout of the MUL1 gene significantly increased apoptosis and enhanced the sensitivity of the OC cell line A2780 to cisplatin. Through this study, we have provided strong evidence for further research on prognostic risk factors and individualized treatment in OC patients, and provided new insights into addressing platinum resistance in OC.
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Biomarcadores Tumorais , Cisplatino , Resistencia a Medicamentos Antineoplásicos , Mitocôndrias , Neoplasias Ovarianas , Humanos , Resistencia a Medicamentos Antineoplásicos/genética , Cisplatino/farmacologia , Feminino , Linhagem Celular Tumoral , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/patologia , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Mitocôndrias/genética , Mitocôndrias/metabolismo , Regulação Neoplásica da Expressão Gênica , Apoptose/efeitos dos fármacos , Apoptose/genética , Antineoplásicos/farmacologia , PrognósticoRESUMO
Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.The aim of this study was to compare overall survival between open and minimally invasive radical hysterectomy with participants followed for 4.5 years. The primary objective was to evaluate whether minimally invasive surgery was noninferior in disease-free survival (DFS) to abdominal radical hysterectomy. Secondary outcomes included overall survival. Sample size was based on DFS of 90% at 4.5 years and 7.2% noninferiority margin for minimally invasive surgery. A total of 631 patients were enrolled: 319 assigned to minimally invasive and 312 to open surgery. Of these, 289 (90.6%) patients underwent minimally invasive surgery and 274 (87.8%) patients open surgery. At 4.5 years, DFS was 85.0% in the minimally invasive group and 96% in the open group (difference of -11.1; 95% CI, -15.8 to -6.3; P = .95 for noninferiority). Minimally invasive surgery was associated with lower rate of DFS compared with open surgery (hazard ratio [HR], 3.91 [95% CI, 2.02 to 7.58]; P < .001). Rate of overall survival at 4.5 years was 90.6% versus 96.2% for the minimally invasive and open surgery groups, respectively (HR for death of any cause = 2.71 [95% CI, 1.32 to 5.59]; P = .007). Given higher recurrence rate and worse overall survival with minimally invasive surgery, an open approach should be standard of care.
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Histerectomia , Procedimentos Cirúrgicos Minimamente Invasivos , Estadiamento de Neoplasias , Neoplasias do Colo do Útero , Humanos , Feminino , Histerectomia/métodos , Histerectomia/mortalidade , Pessoa de Meia-Idade , Neoplasias do Colo do Útero/cirurgia , Neoplasias do Colo do Útero/mortalidade , Neoplasias do Colo do Útero/patologia , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Procedimentos Cirúrgicos Minimamente Invasivos/mortalidade , Adulto , Intervalo Livre de Doença , IdosoRESUMO
Background: Niraparib significantly prolonged progression-free survival versus placebo in patients with platinum-sensitive, recurrent ovarian cancer (PSROC), regardless of germline BRCA mutation (gBRCAm) status, in NORA. This analysis reports final data on overall survival (OS). Methods: This randomised, double-blind, placebo-controlled, phase 3 trial enrolled patients across 30 centres in China between 26 September 2017 and 2 February 2019 (clinicaltrials.gov, NCT03705156). Eligible patients had histologically confirmed, recurrent, (predominantly) high-grade serous epithelial ovarian cancer, fallopian tube carcinoma, or primary peritoneal carcinoma (no histological restrictions for those with gBRCAm) and had received ≥2 prior lines of platinum-based chemotherapy. Patients were randomised (2:1) to receive niraparib or placebo, with stratification by gBRCAm status, time to recurrence following penultimate platinum-based chemotherapy, and response to last platinum-based chemotherapy. Following a protocol amendment, the starting dose was individualised: 200 mg/day for patients with bodyweight <77 kg and/or platelet count <150 × 103/µL at baseline and 300 mg/day otherwise. OS was a secondary endpoint. Findings: Totally, 265 patients were randomised to receive niraparib (n = 177) or placebo (n = 88), and 249 (94.0%) received an individualised starting dose. As of 14 August 2023, median follow-up for OS was 57.9 months (IQR, 54.8-61.6). Median OS (95% CI) with niraparib versus placebo was 51.5 (41.4-58.9) versus 47.6 (33.3-not evaluable [NE]) months, with hazard ratio [HR] of 0.86 (95% CI, 0.60-1.23), in the overall population; 56.0 (36.1-NE) versus 47.6 (31.6-NE) months, with HR of 0.86 (95% CI, 0.46-1.58), in patients with gBRCAm; and 46.5 (41.0-NE) versus 46.9 (31.8-NE) months, with HR of 0.87 (95% CI, 0.56-1.35), in those without. No new safety signals were identified, and myelodysplastic syndromes/acute myeloid leukaemia occurred in three (1.7%) niraparib-treated patients. Interpretation: Niraparib maintenance therapy with an individualised starting dose demonstrated a favourable OS trend versus placebo in PSROC patients, regardless of gBRCAm status. Funding: Zai Lab (Shanghai) Co., Ltd; National Major Scientific and Technological Special Project for "Significant New Drugs Development" in 2018, China [grant number 2018ZX09736019].
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OBJECTIVE: The objective of this study was to explore the clinical significance of survivin expression in epithelial ovarian cancer (EOC) and the effect of survivin small hairpin RNA (shRNA) on survivin expression, apoptosis, and chemosensitivity in the human ovarian cancer cell line OVCAR3. METHODS: A retrospective review of 90 consecutive EOC patients with a median follow-up time of 51 months was conducted. Survivin expression was examined by immunohistochemistry. OVCAR3 cells were transfected in vitro with survivin shRNA. Survivin mRNA expression levels were detected using reverse transcription-polymerase chain reaction. Flow cytometry was applied to determine survivin protein expression levels and cell apoptotic rates. The MTT method was used to examine the effects of survivin shRNA on chemosensitivity in OVCAR3 cells. RESULTS: Positive cytoplasmic expression of survivin was associated with advanced International Federation of Gynecology and Obstetrics (FIGO) stage, nonmucinous type, high grade, and recurrence. Positive survivin expression was also associated with platinum resistance (r = 0.306, P = 0.003). Statistical results indicated that FIGO stage (hazard rate = 1.649, P = 0.047) and cytoplasmic expression of survivin (hazard rate = 1.734, P = 0.010) were independent prognostic factors. Survivin mRNA and protein levels were lower in OVCAR3S (ovarian cancer cells transfected with a survivin recombinant vector) cells at 24 hours after transfection as compared with controls. The flow cytometric analysis revealed that survivin shRNA induced accumulation of cells in the G0/Gl phase, with a decrease in G2/M phase cells following 24 hours of culture as compared with a nontransfected group (P < 0.01). Furthermore, survivin shRNA increased the sensitivity of OVCAR3 cells to paclitaxel 15-fold (P < 0.05), whereas it had no significant effect on cisplatin (P > 0.05). CONCLUSIONS: In addition to FIGO stage, cytoplasmic survivin protein expression is an independent molecular marker for predicting EOC prognosis. Sequence-specific shRNA targeting survivin can effectively suppress survivin expression, enhance apoptosis, and increase the sensitivity of ovarian cancer cells to paclitaxel but not to cisplatin.
Assuntos
Antineoplásicos/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/genética , Proteínas Inibidoras de Apoptose/genética , Neoplasias Epiteliais e Glandulares/diagnóstico , Neoplasias Epiteliais e Glandulares/tratamento farmacológico , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/tratamento farmacológico , Adulto , Idoso , Apoptose/efeitos dos fármacos , Apoptose/genética , Carcinoma Epitelial do Ovário , Linhagem Celular Tumoral , Avaliação Pré-Clínica de Medicamentos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Sinergismo Farmacológico , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/fisiologia , Humanos , Proteínas Inibidoras de Apoptose/metabolismo , Proteínas Inibidoras de Apoptose/fisiologia , Pessoa de Meia-Idade , Neoplasias Epiteliais e Glandulares/metabolismo , Neoplasias Ovarianas/metabolismo , Paclitaxel/administração & dosagem , Paclitaxel/uso terapêutico , Prognóstico , RNA Interferente Pequeno/administração & dosagem , RNA Interferente Pequeno/farmacologia , Estudos Retrospectivos , Survivina , Adulto JovemRESUMO
Development of new anti-counterfeiting technology to increase the difficulty of imitation and decoding is becoming increasingly important, but still remains challenging yet. In this work, we report the design of new fluorescence photoswitches based on photochromic tungsten oxide quantum dots (WO3 QDs) for dual-mode anti-counterfeiting applications. Complexing photochromic WO3 QDs with fluorescent gold nanoclusters (AuNCs) enables the construction of a photoswitchable fluorescence system (WO3-AuNCs) based on fluorescence resonance energy transfer. Detailed spectral and photophysical characterization showed that WO3 QDs well-retain the photochromic properties within the WO3-AuNCs composite. Importantly, photoresponsive and highly reversible switching of both color and fluorescence signals was successfully achieved by simply alternating the irradiation with UV and visible light. Potential utility of photoswitchable WO3-AuNCs composite as novel dual-mode anti-counterfeiting materials has been successfully demonstrated, including photoswitchable ink, rewritable paper and number encryption. Compared with other anti-counterfeiting materials, the present photochromic WO3 QDs-based fluorescent switches are easily synthesized and handled, and they can provide dual security mode (color and fluorescence). This work provides a generable WO3 QDs-assisted strategy of fabricating advanced fluorescence photoswitches for versatile optical counterfeiting applications.
RESUMO
To address the issue posed by drug-resistant bacteria and inspired by natural antimicrobial enzymes, we report the atomically doped copper on guanine-derived nanosheets (G-Cu) that possess the integrated catalytic cascade property of glucose oxidase and peroxidase, yielding free radicals to eliminate drug-resistant bacteria upon light irradiation. Density functional theory calculations demonstrate that copper could notably promote oxygen activation and H2O2 splitting on the G-Cu complexes. Further all-atom simulation and experimental data indicate that the lysis of bacteria is mainly induced by cell membrane damage and the elevation of intracellular reactive oxygen species. Lastly, the G-Cu complexes efficiently eliminate the staphylococci in the infected wounds and accelerate their closure in a murine model, with negligible side effects on the normal tissues. Therefore, our G-Cu complexes may provide an efficient nonantibiotic alternative to the current treatments for bacterial infections.