Although receptor status including estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) of the primary breast tumors was related to the prognosis of ...breast cancer patients, little information is yet available on whether patient management and survival are impacted by receptor conversion in breast cancer metastases. Using data from the nation‐wide multicenter clinical epidemiology study of advanced breast cancer in China (NCT03047889), we report the situation of retesting ER, PR and HER2 status for breast cancer metastases and evaluate the patient management and prognostic value of receptor conversion. In total, 3295 patients were analyzed and 1583 (48.0%) patients retesting receptor status for metastasis. Discordance in one or more receptors between the primary and the metastatic biopsy was found in 37.7% of women. Patients who remained hormone receptor (HR) positive in their metastases had similar progression‐free survival of first‐line and second‐line treatment compared to patients with HR conversion (P > .05). In multivariate analysis, patients who showed ER conversion from negative to positive had longer disease‐free survival (DFS) than patients who remained negative in their metastases (hazard ratio, 2.05; 95% confidence interval CI, 1.45‐2.90; P < .001). Patients with PR remained positive and had longer DFS than patients with PR conversion from negative to positive (hazard ratio, 0.56; 95% CI, 0.38‐0.83; P = .004). Patients with PR conversion have shorter overall survival than patients with PR remained positive or negative (P = .016 and P = .041, respectively). Our findings showed that the receptors' conversions were common in metastatic breast cancer, and the conversion impacted the survival.
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Tumor metastasis is still the main cause of breast cancer mortality. Treatment of metastatic tumors is often based on the hormone receptor and human epidermal growth factor receptor 2 status of the primary tumor. However, as many as a third of patients with metastases have altered receptor status. Does this receptor conversion affect prognosis? In this large Chinese study, the authors found that, in many cases, the answer is yes. These results indicate that it is clinically important to biopsy distant metastases and assess receptor status whenever possible and to use these results to guide treatment.
Despite great achievements in sensitive and selective detection of important biomolecules in living cells, it is still challenging to develop smart and controllable sensing nanodevices for cellular ...studies that can be activated at desired time in target sites. To address this issue, we have constructed a remote-controlled “lock–unlock” nanosystem for visual analysis of endogenous potassium ions (K+), which employed a dual-stranded aptamer precursor (DSAP) as recognition molecules, SiO2 based gold nanoshells (AuNS) as nanocarriers, and near-infrared ray (NIR) as the remotely applied stimulus. With the well-designed and activatable DSAP-AuNS, the deficiencies of traditional aptamer-based sensors have been successfully overcome, and the undesired response during transport has been avoided, especially in complex physiological microenvironments. While triggered by NIR, the increased local temperature of AuNS induced the dehybridiztion of DSAP, realized the “lock–unlock” switch of the DSAP-AuNS nanosystem, activated the binding capability of aptamer, and then monitored intracellular K+ via the change of fluorescence signal. This DSAP-AuNS nanosystem not only allows us to visualize endogenous ions in living cells at a desired time but also paves the way for fabricating temporal controllable nanodevices for cellular studies.
In this study, we have developed a programmable electrochemiluminescence (ECL) system based on multi-segmented CdS-Au nanorod arrays with a sequential and highly tunable structure. The nanorod arrays ...were synthesized by an electrodeposition method using anodic aluminum oxide (AAO) as the template in which the Au and CdS segments were alternately electrodeposited. Compared to pure CdS nanorod arrays, multi-segmented CdS-Au nanorod arrays have showed a better ECL performance, which can be attributed to two factors: the favorable electron transfer and the surface plasma resonance (SPR) effect of the Au segment. On the one hand, we demonstrated that the Au segment can increase the charge transfer rate of CdS, which is beneficial for the ECL process because the generation of the radical state needs to accept electrons and then generate the radical state. On the other hand, the SPR of Au plasmon-induced local electromagnetic field enhancement can increase the radiative decay rate of CdS which makes the ECL process more efficient and lead to a higher ECL intensity. And also, an ECL sensor with multi-segmented CdS-Au nanorod arrays was constructed to detect prostate protein antigen (PSA). This study provides some basis for designing high-performance ECL emission materials and the construction of biosensors.
To evaluate the clinical efficacy of a combination treatment of traditional Chinese medicine (TCM) in scalp seborrheic dermatitis (SSD) of differing severity.
Our study included patients with typical ...SSD who visited the Medical Research Center for Hair and Skin at our hospital. Symptoms were evaluated using a "16-point scale" developed at the center. Patients who had mild SSD were treated with Pi Fu Kang Xi Ye (PFKXY), those with moderate SSD were treated with PFKXY combined with Run Zao Zhi Yang Jiao Nang (RZZYJN), and those with severe dermatitis were treated with PFKXY and RZZYJN along with garlicin enteric-coated tablets. Patients were asked to revisit 4 weeks later to evaluate the efficacy.
Symptom scores of all patients decreased by (5.48 ± 2.51) after treatment as compared with before treatment, and the results of t-test and correlation test were significant (p < 0.01). The scores of patients with mild, moderate and severe SSD decreased by 3.14 ± 1.83, 4.90 ± 1.77, and 8.05 ± 2.21, respectively, after treatment as compared with before treatment. Among them, the changes in scores of patients with moderate dermatitis before and after treatment were significant in the t-test and correlation test (p < 0.01).
In this study, the combination treatment of TCM showed significant efficacy in the treatment of mild, moderate, and severe SSD, and the efficacy was stable, especially for patients with moderate SSD.
Tetrahydroxy bile acids (THBAs) are hydrophilic and are present at minimal or undetectable levels in healthy human adults, but are present at high levels in bile salt export pump (abcb11)-knockout ...mice. The roles of THBAs in human cholestatic diseases are unclear. We aimed to investigate the presence of THBAs in patients with infantile intrahepatic cholestasis and its correlation with outcome. Urinary bile acids (BAs) were analyzed by GC-MS. Data were compared between good (n = 21) (disease-free before 1 year old) and poor prognosis groups (n = 19). Good prognosis patients had a higher urinary THBA proportion than poor prognosis patients 25.89% (3.45–76.73%) vs. 1.93% (0.05–48.90%). A urinary THBA proportion >7.23% predicted good prognosis with high sensitivity (95.24%), specificity (84.21%), and area under the curve (0.91) (P < 0.0001). A THBA proportion ≤7.23% was an independent factor for decreased transplant-free survival (hazard ratio = 7.16, confidence interval: 1.24–41.31, P = 0.028). Patients with a confirmed ABCB11 or tight junction protein 2 gene mutation (n = 7) had a minimally detectable THBA proportion (0.23–2.99% of total BAs). Three patients with an ATP8B1 mutation had an elevated THBA proportion (7.51–37.26%). In conclusion, in addition to disease entity as a major determinant of outcome, a high THBA level was associated with good outcome in the infantile intrahepatic cholestasis patients.
Fever can occur after acute myocardial infarction (MI). The influence of body temperature (BT) after hospital arrival on patients with acute MI has rarely been investigated.
Patients who were ...diagnosed with acute MI in the emergency department (ED) of a tertiary teaching hospital between 1 January 2020 and 31 December 2020 were enrolled. Based on the tympanic temperature obtained at the ED triage, patients were categorized into normothermic (35.5°C-37.5°C), hypothermic (< 35.5°C), or hyperthermic (> 37.5°C) groups. The primary outcome was in-hospital cardiac arrest (IHCA), while the secondary outcomes were adverse events. Statistical significance was set at p < 0.05.
There were 440 enrollees; significant differences were found among the normothermic (n = 369, 83.9%), hypothermic (n = 27, 6.1%), and hyperthermic (n = 44, 10.0%) groups in the triage respiratory rate (median IQR) (20.0 4.0 cycles/min versus 20.0 4.0 versus 20.0 7.5, p = 0.009), triage heart rate (88.0 29.0 beats/min versus 82.0 28.0 versus 102.5 30.5, p < 0.001), presence of ST-elevation MI (42.0% versus 66.7% versus 31.8%, p = 0.014), need for cardiac catheterization (87.3% versus 85.2% versus 72.7%, p = 0.034), initial troponin T level (165.9 565.2 ng/L versus 49.1 202.0 versus 318.8 2002.0, p = 0.002), peak troponin T level (343.8 1405.9 ng/L versus 218.7 2318.2 versus 832.0 2640.8, p = 0.003), length of ICU stay (2.0 3.0 days versus 3.0 8.0 versus 3.0 9.5, p = 0.006), length of hospital stay (4.0 4.5 days versus 6.0 15.0 versus 10.5 10.8, p < 0.001), and infection during hospitalization (19.8% versus 29.6% versus 63.6%, p < 0.001) but not in IHCA (7.6% versus 14.8% versus 11.4%, p = 0.323) or any adverse events (50.9% versus 48.1% versus 63.6%, p = 0.258). Multivariable analysis showed no significant association of triage BT with IHCA or any major complication.
Triage BT did not show a significant association with IHCA or adverse events in patients with acute MI. However, triage BT could be associated with different clinical presentations and should warrant further investigation.
Taiwan is one of the endemic regions where upper tract urothelial carcinoma (UTUC) accounts for approximately a third of all urothelial tumors. Owing to its high prevalence, extensive experience has ...been accumulated in minimally invasive radical nephroureterectomy (RNU). Although a variety of predictive factors have been explored in numerous studies, most of them were on a single-center or limited institutional basis and data from a domestic cohort are lacking.
This study aims to identify significant predicting factors of oncological outcomes, including overall survival (OS), cancer-specific survival (CSS), disease-free survival (DFS), and intravesical recurrence-free survival (IVRFS), following RNU for UTUC in Taiwan.
A multicenter registry database, Taiwan UTUC Collaboration Group, was utilized to analyze oncological outcomes of 3,333 patients undergoing RNU from 1988 to 2021 among various hospitals in Taiwan. Clinicopathological parameters were recorded according to the principles established by consensus meetings. The Kaplan-Meier estimator was utilized to estimate the survival rates, and the curves were compared using the stratified log-rank test. Univariate and multivariate analyses were performed with the Cox proportional hazard model to explore potential predicting factors.
With a median follow-up of 41.8 months in 1,808 patients with complete information, the 5-year IVRFS, DFS, CSS, and OS probabilities were 66%, 72%, 81%, and 70%, respectively. In total, 482 patients experienced intravesical recurrence, 307 died of UTUC, and 583 died of any cause. Gender predominance was female (57%). A total of 1,531 patients (84.7%) had high-grade tumors; preoperative hydronephrosis presented in 1,094 patients (60.5%). Synchronous bladder UC was identified in 292 patients (16.2%). Minimally invasive procedures accounted for 78.8% of all surgeries, including 768 hand-assisted laparoscopic (42.5%) and 494 laparoscopic (27.3%) approaches. Synchronous bladder UC was the dominant adverse predicting factor for all survival outcomes. Other independent predicting factors for OS, CSS, and DFS included age ≧70, presence of preoperative hydronephrosis, positive surgical margin, LVI, pathological T and N staging, and laparoscopic RNU.
Synchronous UC of the urinary bladder is an independent adverse prognostic factor for survival in UTUC. The presence of preoperative hydronephrosis was also corroborated as a disadvantageous prognostic factor. Our multivariate analysis suggested that laparoscopic RNU might provide better oncological control.
This study aimed to compare the oncological outcomes of patients with upper tract urothelial carcinoma (UTUC) without clinical lymph node metastasis (cN0) undergoing lymph node dissection (LND) ...during radical nephroureterectomy (NU).
From the updated data of the Taiwan UTUC Collaboration Group, a total of 2726 UTUC patients were identified. We only include patients with ≥ pT2 stage and enrolled 658 patients. The Kaplan-Meier estimator and Cox proportional hazards model were used to analyze overall survival (OS), cancer-specific survival (CSS), disease-free survival (DFS), and bladder recurrence-free survival (BRFS) in LND (+) and LND (-) groups.
A total of 658 patients were included and 463 patients without receiving LND and 195 patients receiving LND. From both univariate and multivariate survival analysis, there are no significant difference between LND (+) and LND (-) group in survival rate. In LND (+) group, 18.5% patients have pathological LN metastasis. After analyzing pN+ subgroup, it revealed worse CSS (p = 0.010) and DFS (p < 0.001) compared with pN0 patients.
We found no significant survival benefit related to LND in cN0 stage, ≥ pT2 stage UTUC, irrespective of the number of LNs removed, although pN+ affected cancer prognosis. However, from the result of pN (+) subgroup of LND (+) cohort analysis, it may be reasonable to not perform LND in patients with cT2N0 stage due to low positive predictive value of pN (+). In addition, performing LND may be considered for ureter cancer, which tends to cause lymphatic and hematogenous tumor spreading. Further large prospective studies are needed to validate our findings.
This work reports the use of compositionally heterogeneous asymmetric Ag@Au core–satellite nanoassembly functionalized with DNA sequence as unique signaling nanoprobes for the realization of new ...energy-transfer-based photoelectrochemical (PEC) immunoassay of prostate- specific antigen (PSA). Specifically, the Ag@Au asymmetric core–satellite nanoassemblies (Ag@Au ACS) were fabricated on a two-dimensional glass substrate by a modified controlled assembly technique, and then functionalized with DNA sequences containing PSA aptamers as signaling nanoprobes. Then, the sandwich complexing between the PSA, its antibodies, and the signaling nanoprobes was performed on a CdS QDs modified indium tin oxide (ITO) electrode. The single stranded DNA can server as a facile mediator that place the Ag@Au ACS in proximity of CdS QDs, stimulating the interparticle exciton–plasmon interactions between Ag@Au ACS and CdS QDs and thus quenching the excitonic states in the latter. Since the damping effect is closely related to the target concentration, a novel energy-transfer-based PEC bioanalysis could be achieved for the sensitive and specific PSA assay. The developed biosensor displayed a linear range from 1.0×10−11gmL−1 to 1.0×10−7gmL−1 and the detection limit was experimentally found to be of 0.3×10–13gmL−1. This strategy used the Ag@Au ACS-DNA signaling nanoprobes and overcame the deficiency of short operating distance of the energy transfer process for feasible PEC immunoassay. More significantly, it provided a way to couple the plasmonic properties of the Ag NPs and Au NPs in a single PEC bioanalytical system. We expected this work could inspire more interests and further investigations on the advanced engineering of the core–satellite or other judiciously designed nanostructures for new PEC bioanalytical uses with novel properties.
•Ag@Au asymmetric core–satellite nanoassembly was fabricated.•It was then applied for the novel energy-transfer-based PEC immunoassay.•The proposed format could serve as a general basis for PEC bioanalysis.
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