Evaluation of the Efficacy of Postoperative Adjuvant Therapy for HER2-Positive Ductal Carcinoma in Situ with Microinvasion.

A retrospective study on 90 eligible HER2+ ductal carcinoma in situ with microinvasion (DCIS-MI) patients was performed with a median follow-up time of 57 months. The baseline was consistent between the 4-cycle and 6-cycle chemotherapy groups. There were more patients with multiple foci of micrometastasis in the target therapy group in the two groups with or without target therapy (p < 0.01). Postoperative chemotherapy with a 4-cycle regimen can achieve the expected therapeutic effect in patients with HER2+ DCIS-MI, but the role of target therapy in HER2+ DCIS-MI patients has not been confirmed.

The role of m6A methylation in therapy resistance in cancer.

Cancer therapy resistance is the main cause of cancer treatment failure. The mechanism of therapy resistance is a hot topic in epigenetics. As one of the most common RNA modifications, N6-methyladenosine (m6A) is involved in various processes of RNA metabolism, such as stability, splicing, transcription, translation, and degradation. A large number of studies have shown that m6A RNA methylation regulates the proliferation and invasion of cancer cells, but the role of m6A in cancer therapy resistance is unclear. In this review, we summarized the research progress related to the role of m6A in regulating therapy resistance in cancers.

Nomogram prediction for the risk of venous thromboembolism in patients with lung cancer.

OBJECTIVE: The aim of this study was to establish a nomogram graph model to accurately predict the venous thromboembolism (VTE) risk probability in the general population with lung cancer. METHODS: Based on data from patients with lung cancer in Chongqing University Cancer Hospital of China, the independent risk factors of VTE were identified by the logistic univariable and multivariable analysis and were integrated to construct a nomogram, which was validated internally. The predictive effectiveness of the nomogram was evaluated by the receiver operating characteristic curve (ROC) and calibration curve. RESULTS: A total of 3398 lung cancer patients were included for analysis. The nomogram incorporated eleven independent VTE risk factors including karnofsky performance scale (KPS), stage of cancer, varicosity, chronic obstructive pulmonary disease (COPD), central venous catheter (CVC), albumin, prothrombin time (PT), leukocyte counts, epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), dexamethasone, and bevacizumab. The C-index of the nomogram model was 0.843 and 0.791 in the training and validation cohort, respectively, demonstrating good discriminative power. The calibration plots of the nomogram revealed excellent agreement between the predicted and actual probabilities. CONCLUSIONS: We established and validated a novel nomogram for predicting the risk of VTE in patients with lung cancer. The nomogram model could precisely estimate the VTE risk of individual lung cancer patients and identify high-risk patients who are in need of a specific anticoagulation treatment strategy.

Repeated-sprint training in hypoxia boosts up team-sport-specific repeated-sprint ability: 2-week vs 5-week training regimen.

PURPOSE: To investigate (1) the boosting effects immediately and 4 weeks following 2-week, 6-session repeated-sprint training in hypoxia (RSH2-wk, n = 10) on the ability of team-sport players in performing repeated sprints (RSA) during a team-sport-specific intermittent exercise protocol (RSAIEP) by comparing with normoxic counterpart (CON2-wk, n = 12), and (2) the dose effects of the RSH by comparing the RSA alterations in RSH2-wk with those resulting from a 5-week, 15-session regimen (RSH5-wk, n = 10). METHODS: Repeated-sprint training protocol consisted of 3 sets, 5 × 5-s all-out sprints on non-motorized treadmill interspersed with 25-s passive recovery under the hypoxia of 13.5% and normoxia, respectively. The within- (pre-, post-, 4-week post-intervention) and between- (RSH2-wk, RSH5-wk, CON2-wk) group differences in the performance of four sets of RSA tests held during the RSAIEP on the same treadmill were assessed. RESULTS: In comparison with pre-intervention, RSA variables, particularly the mean velocity, horizontal force, and power output during the RSAIEP enhanced significantly immediate post RSH in RSH2-wk (5.1-13.7%), while trivially in CON2-wk (2.1-6.2%). Nevertheless, the enhanced RSA in RSH2-wk diminished 4 weeks after the RSH (- 3.17-0.37%). For the RSH5-wk, the enhancement of RSA immediately following the 5-week RSH (4.2-16.3%) did not differ from that of RSH2-wk, yet the enhanced RSA was well-maintained 4-week post-RSH (0.12-1.14%). CONCLUSIONS: Two-week and five-week RSH regimens could comparably boost up the effects of repeated-sprint training in normoxia, while dose effect detected on the RSA enhancement was minimal. Nevertheless, superior residual effects of the RSH on RSA appear to be associated with prolonged regimen.

Analysis of Factors Influencing the Prognosis of Periodontal Disease Treated with Host Modulation and the Development of a Predictive Model.

Objective: To explore the effect of host regulation (HMT) therapy on periodontal disease and construct prognosis prediction model. Methods: The clinical data of 106 patients who received HMT treatment in our hospital from January 2020 to January 2023 were retrospectively analyzed. The changes of plaque index (PLI), periodontal pocket depth (PD), tooth looseness (TM), attachment loss (AL) and gingival bleeding index (BI) were observed before and after treatment. According to the clinical efficacy of patients after treatment, they were divided into effective group and ineffective group. Multivariate Logistic regression model was used to analyze the relevant factors affecting the prognosis of patients., and a predictive model of the factors affecting the prognosis of periodontal disease was constructed to predict the diagnostic value of the prognostic outcome of periodontal disease using the relative operating characteristic (ROC) curve. Results: After HMT treatment, PLI, PD, AL and BI were significantly reduced in all patients, while TM(grade II and III) patients were decreased (P < .05). After 4 weeks of treatment, a total of 74 patients were included in the effective group. Univariate and multivariate analysis showed that oral hygiene, early use of broad-spectrum antibiotics, periodontal bone loss shape, gingival flap thickness and alveolar bone resorption type were independent factors influencing the prognosis of HMT (P < .001). ROC results showed that the area under the curve (AUC), sensitivity and specificity of the above independent influencing factors combined to predict the clinical efficacy of HMT in patients with periodontal disease were higher. Conclusion: HMT has a good clinical effect in the treatment of periodontal disease, but there are still cases of poor prognostic effect. The combination of independent factors affecting the prognosis of HMT has a good predictive value for the clinical efficacy of patients with periodontal disease after HMT treatment.

Cytokines screening identifies MIG (CXCL9) for postoperative recurrence prediction in operated non-small cell lung cancer patients.

BACKGROUND: Exploration of reliable biomarkers most likely to identify non-small cell lung cancer (NSCLC) patients at high risk for recurrence after surgery is needed. METHODS: Quantibody® Human Cytokine Antibody 6000 was used as screening tool to measure serum levels of 280 cytokines in ten healthy individuals and nine samples from three NSCLC patients before operation, after operation and postoperative recurrence. Selected cytokines were validated in two independent sets (89 patients before surgery, 69 patients after surgery and 40 patients with postoperative recurrence for each set) using ELISA method. The association of the selected cytokine with clinicopathologic features was also evaluated. RESULTS: Thirty-six cytokines were declined after surgery and again elevated when recurrence. We selected MIG to be further assessed in 2 validation sets, the mean value of serum MIG levels in 396 NSCLC patients was 253.42 ± 274.48 pg/mL and was significantly higher than the level in 60 healthy controls (47.65 ± 33.23 pg/mL, P < 0.0001). The serum MIG levels were 366.36 ± 324.04 pg/mL pre-operation, 134.04 ± 127.52 pg/mL post-operation and 208.05 ± 239.39 pg/mL in recurrence in NSCLC patients. The serum MIG levels were significant differences among NSCLC patients of pre-operation, post-operation and recurrence and controls (P < 0.0001). Moreover, Serum MIG levels were decreased markedly after operation and notably increased when disease relapsed (P < 0.0005). Serum MIG levels trend to be higher in patients with male gender, older age, smoking habit, poor tumor differentiation, and non-adenocarcinoma histology. CONCLUSIONS: These data indicated that MIG might be an indicator of postoperative recurrence and help to identify NSCLC patient who was easy to relapse after surgery.

An ultrasensitive hairpin sensor based on g-C3N4 nanocomposite for the detection of miRNA-155 in breast cancer patient serum.

Achieving the early diagnosis of breast cancer, through ultrasensitive detection of tumor marker miRNA-155, is a significant challenge. Therefore, an ultrasensitive hairpin electrochemical biosensor based on graphite-like phase carbon nitride composite was proposed. In this paper, poly(D-glucosamine) (PDG) was used as a stabilizer and reducing agent to prepare gold nanoparticles at room temperature, and then a graphite-like phase with a two-dimensional lamellar structure carbon nitride was further combined with it to obtain the poly(D-glucosamine)/gold nanoparticles/graphite-like phase carbon nitride nanocomposite (PDG/AuNPs/g-C3N4), in order to achieve the goal of signal amplification. The specific hairpin capture probe (HP) that recognized and bound miRNA-155 was then grafted. The hairpin biosensor showed a linear range of 0.1 fM-1 pM with a detection limit of 0.05 fM using differential pulse voltammetry (DPV) electrochemical analysis. Furthermore, the excellent performance hairpin electrochemical biosensor had been applied to the detection of miRNA-155 in human serum samples with good recovery.

Advancements in electrochemical biosensing for respiratory virus detection: A review.

Respiratory viruses are real menace for human health which result in devastating epidemic disease. Consequently, it is in urgent need of identifying and quantifying virus with a rapid, sensitive and precise approach. The study of electrochemical biosensors for respiratory virus detection has become one of the most rapidly developing scientific fields. Recent developments in electrochemical biosensors concerning respiratory virus detection are comprehensively reviewed in this paper. This review is structured along common detecting objects of respiratory viruses, electrochemical biosensors, electrochemical biosensors for respiratory virus detection and future challenges. The electrochemical biosensors for respiratory virus detection are introduced, including nucleic acids-based, immunosensors and other affinity biosensors. Lastly, for Coronavirus disease 2019 (COVID-19) diagnosis, the future challenges regarding developing electrochemical biosensor-based Point-of-Care Tests (POCTs) are summarized. This review is expected to provide a helpful guide for the researchers entering this interdisciplinary field and developing more novel electrochemical biosensors for respiratory virus detection.

Relationship between periodontal disease and male infertility: A case-control study.

OBJECTIVES: To compare the prevalence of chronic periodontitis between men who had semen abnormalities and those who had normozoospermia through a case-control study. MATERIALS AND METHODS: Male patients who visited the assisted reproduction clinic of a large general hospital and were diagnosed with semen abnormalities were included in the case group. The control group was composed of patients of the same clinic with normozoospermia. The semen analysis included sperm concentration, count and progressive and total motility, which were measured in the laboratory. A questionnaire and clinical periodontal examination were conducted for all participants. Logistic regression was performed to explore the relationship between chronic periodontitis and male infertility. RESULTS: A total of 192 participants were included: 63 participants (32.8%) had some type of semen abnormality (case group), while 129 participants (67.2%) had normozoospermia (control group). The case group had a significantly higher prevalence of moderate/severe periodontitis than the control group (33.3% vs. 17.8%, p = .012). The logistic regression showed that participants who had moderate/severe periodontitis had a greater chance of having semen abnormalities after adjusting for other confounding factors (OR = 3.377, p = .005). CONCLUSIONS: Periodontitis is associated with semen abnormalities and sperm motility in men.

Trend on dental caries status and its risk indicators in children aged 12 years in China: a multilevel analysis based on the repeated national cross-sectional surveys in 2005 and 2015.

BACKGROUND: This study aimed to explore the trend and risk indicators for dental caries of children aged 12 years in China based on national oral health survey data in 2005 and 2015. METHODS: Research data were from the two latest national oral health surveys conducted in mainland China, including 30 and 31 provinces, autonomous regions, and municipalities in 2005 and 2015, respectively. Children aged 12 years were clinically examined for dental caries and dental fluorosis according to the World Health Organization criteria. Sociodemographic characteristics and oral health-related behaviours were collected using questionnaires. Multilevel zero-inflated negative binomial regression model was used to investigate the association between dental caries severity and dental fluorosis, sociodemographic characteristics, and oral health-related behaviours. RESULTS: The final analyses included 12,350 and 27,818 children surveyed in 2005 and 2015, respectively. The standardized prevalence of dental caries increased from 27.05% (95% confidence interval [CI], 24.25-28.85) in 2005 to 37.92% (95% CI, 34.94-40.90) in 2015, and the respective standardized mean decayed, missing, filled teeth (DMFT) index scores increased from 0.50 (standard deviation [SD], 1.04) to 0.83 (SD, 1.45) (P < 0.001). Fujian province had the highest increase in dental caries, followed by Liaoning, Heilongjiang, Hainan, and Yunnan. Results revealed that children who were girls, more frequently experienced dental pain, and had more recent dental visits, had significantly higher DMFT scores after adjusting for the survey year and other variables (all P < 0.05). CONCLUSIONS: Dental caries of 12-year-old children in China deteriorated from 2005 to 2015, particularly in the northeast and southwest regions. Dental caries was associated with sex, dental pain, and dental service utilization.

Simultaneous sex and species classification of silkworm pupae by NIR spectroscopy combined with chemometric analysis.

BACKGROUND: Most studies only focus on the sex discrimination of silkworm pupae. However, species differentiation of silkworm pupae is also needed in sericulture. To classify the sex and species at the same time, the present study adopts near infrared (NIR) spectroscopy combined with multivariate analysis. RESULTS: First, spectra samples were acquired using an NIR sensor, comprising female and male silkworm pupae from three species. Second, three different variables selection approaches were used, including a successive projections algorithm, competitive adaptive reweighted sampling (CARS) and interval partial least squares (iPLS). Third, identification models were built based on random forest and partial least squares discriminant analysis (PLSDA). The experimental results show that iPLS-PLSDA model (95.24%) gives a high performance when using the one of the three variable selection methods alone. To further increase the performance, the variable selection methods are optimized. The accuracy of the iPLS-CARS-PLSDA model is as high as 98.41%. CONCLUSION: The present study demonstrates that the optimized variable selection method in combination with NIR spectroscopy represents a suitable strategy for sex and species identification of silkworm pupae. © 2020 Society of Chemical Industry.

A novel SWCNT-amplified "signal-on" electrochemical aptasensor for the determination of trace level of bisphenol A in human serum and lake water.

A novel "signal-on" electrochemical aptasensor was developed for ultrasensitive and specific detection of BPA, using single-walled carbon nanotubes (SWCNT) as the electro-catalytic probe for further signal amplification. The multi-walled carbon nanotubes (MWCNT), amino-functionalized magnetite, and gold nanoparticles (NH2-Fe3O4/Au NPs) were applied first to modify the glassy carbon electrode (GCE) surface and to form a nanomaterial film with satisfactory conductive properties, stability, and biocompatibility. The BPA aptamer was then loaded onto the sensing platform by hybridization with complementary DNA (CDNA). In the presence of BPA it combines with the aptamer and the BPA-aptamer conjugate was released from the electrode;subsequently the added SWCNT and CDNA assembled quickly. Thus, the dual-amplification of the "signal-on" electrochemical aptasensor takes effect. The [Fe (CN)6]3-/4- redox probe signal (∆I) detected by DPV (differential pulse voltammetry) is proportional to the negative logarithm of BPA concentration between 10-19 M and 10-14 M. The detection limit is 0.08 aM. Importantly, the proposed biosensor represents a successful application for determination of BPA in human serum and lake water. Schematic representation of SWCNT-amplified "signal-on" electrochemical aptasensor for the detection of trace level of bisphenol A in human serum and lake water.

Probe Sector Matching for Freehand 3D Ultrasound Reconstruction.

A 3D ultrasound image reconstruction technique, named probe sector matching (PSM), is proposed in this paper for a freehand linear array ultrasound probe equipped with multiple sensors, providing the position and attitude of the transducer and the pressure between the transducer and the target surface. The proposed PSM method includes three main steps. First, the imaging target and the working range of the probe are set to be the center and the radius of the imaging field of view, respectively. To reconstruct a 3D volume, the positions of all necessary probe sectors are pre-calculated inversely to form a sector database. Second, 2D cross-section probe sectors with the corresponding optical positioning, attitude and pressure information are collected when the ultrasound probe is moving around the imaging target. Last, an improved 3D Hough transform is used to match the plane of the current probe sector to the existing sector images in the sector database. After all pre-calculated probe sectors are acquired and matched into the 3D space defined by the sector database, a 3D ultrasound reconstruction is completed. The PSM is validated through two experiments: a virtual simulation using a numerical model and a lab experiment using a real physical model. The experimental results show that the PSM effectively reduces the errors caused by changes in the target position due to the uneven surface pressure or the inhomogeneity of the transmission media. We conclude that the PSM proposed in this study may help to design a lightweight, inexpensive and flexible ultrasound device with accurate 3D imaging capacity.

Global Optimal Structured Embedding Learning for Remote Sensing Image Retrieval.

A rich line of works focus on designing elegant loss functions under the deep metric learning (DML) paradigm to learn a discriminative embedding space for remote sensing image retrieval (RSIR). Essentially, such embedding space could efficiently distinguish deep feature descriptors. So far, most existing losses used in RSIR are based on triplets, which have disadvantages of local optimization, slow convergence and insufficient use of similarity structure in a mini-batch. In this paper, we present a novel DML method named as global optimal structured loss to deal with the limitation of triplet loss. To be specific, we use a softmax function rather than a hinge function in our novel loss to realize global optimization. In addition, we present a novel optimal structured loss, which globally learn an efficient deep embedding space with mined informative sample pairs to force the positive pairs within a limitation and push the negative ones far away from a given boundary. We have conducted extensive experiments on four public remote sensing datasets and the results show that the proposed global optimal structured loss with pairs mining scheme achieves the state-of-the-art performance compared with the baselines.

CircHIPK3 sponges miR-558 to suppress heparanase expression in bladder cancer cells.

Increasing evidences suggest that circular RNAs (circRNAs) exert crucial functions in regulating gene expression. In this study, we perform RNA-seq and identify 6,154 distinct circRNAs from human bladder cancer and normal bladder tissues. We find that hundreds of circRNAs are significantly dysregulated in human bladder cancer tissues. We further show that circHIPK3, also named bladder cancer-related circular RNA-2 (BCRC-2), is significantly down-regulated in bladder cancer tissues and cell lines, and negatively correlates with bladder cancer grade, invasion as well as lymph node metastasis, respectively. Over-expression of circHIPK3 effectively inhibits migration, invasion, and angiogenesis of bladder cancer cells in vitro and suppresses bladder cancer growth and metastasis in vivo Mechanistic studies reveal that circHIPK3 contains two critical binding sites for the microRNA miR-558 and can abundantly sponge miR-558 to suppress the expression of heparanase (HPSE). Taken together, our findings provide evidence that circRNAs act as "microRNA sponges", and suggest a new therapeutic target for the treatment of bladder cancer.

Circular RNA BCRC-3 suppresses bladder cancer proliferation through miR-182-5p/p27 axis.

BACKGROUND: Circular RNAs (circRNAs) are a new member of noncoding RNAs (ncRNAs) that have recently been described as key regulators of gene expression. Our previous study had identified the negative correlation between circHIPK3 and bladder cancer grade, invasion, as well as lymph node metastasis. However, the roles of circRNAs in cellular proliferation in bladder cancer remain largely unknown. METHODS: We had analyzed circRNA high-throughout sequencing from human tissues and determined bladder cancer related circRNA-3 (BCRC-3, GenBank: KU921434.1) as a new candidate circRNA derived from PSMD1 gene. The expression levels of circRNAs, mRNAs and miRNAs in human tissues and cells were detected by quantitative real-time PCR (qRT-PCR). The effects of BCRC-3 on cancer cells were explored by transfecting with plasmids in vitro and in vivo. RNA pull down assay, luciferase reporter assay and fluorescence in situ hybridization were applied to verify the interaction between BCRC-3 and microRNAs. Anticancer effects of methyl jasmonate (MJ) were measured by flow cytometry assay, western blot and qRT-PCR. RESULTS: BCRC-3 was lowly expressed in bladder cancer tissues and cell lines. Proliferation of BC cells was suppressed by ectopic expression of BCRC-3 in vitro and in vivo. Mechanistically, overexpression of BCRC-3 induced the expression of cyclin-dependent kinase inhibitor 1B (p27). Importantly, BCRC-3 could directly interact with miR-182-5p, and subsequently act as a miRNA sponge to promote the miR-182-5p-targeted 3'UTR activity of p27. Furthermore, MJ significantly increased the expression of BCRC-3, resulting in an obvious up-regulation of p27. CONCLUSIONS: BCRC-3 functions as a tumor inhibitor to suppress BC cell proliferation through miR-182-5p/p27 axis, which would be a novel target for BC therapy.

A novel electrochemical aptamer-antibody sandwich assay for the detection of tau-381 in human serum.

Tau protein plays a crucial role in the pathogenesis of Alzheimer's disease (AD). However, the assay to detect low concentrations of tau protein is a great challenge for the early diagnosis of AD. We will outline a novel aptamer-antibody sandwich assay based on an electrochemical biosensor for the detection of tau-381 in human serum. To improve the detection sensitivity, the aptamer-antibody sandwich assay for the detection of tau-381 was developed by using a tau antibody (anti-tau) and an aptamer specific to tau-381 as the recognition element and cysteamine-stabilized gold nanoparticles (AuNPs) for signal amplification. Differential pulse voltammetry (DPV) was employed to record the signal response of tau-381 with different concentrations. The tau-381 concentration ranged from 0.5 pM to 100 pM. The responses of DPV measurements showed excellent results in this dynamic range. This simple, rapid, highly sensitive and specific assay gave a low limit of detection (LOD) of 0.42 pM for tau-381. The feasibility and reliability of the assay were verified by testing tau-381 in human serum from patients with AD. Thus, this method could prove valuable in diagnosing AD within the early stages of the disease.

Staged Incentive and Punishment Mechanism for Mobile Crowd Sensing.

Having an incentive mechanism is crucial for the recruitment of mobile users to participate in a sensing task and to ensure that participants provide high-quality sensing data. In this paper, we investigate a staged incentive and punishment mechanism for mobile crowd sensing. We first divide the incentive process into two stages: the recruiting stage and the sensing stage. In the recruiting stage, we introduce the payment incentive coefficient and design a Stackelberg-based game method. The participants can be recruited via game interaction. In the sensing stage, we propose a sensing data utility algorithm in the interaction. After the sensing task, the winners can be filtered out using data utility, which is affected by time⁻space correlation. In particular, the participants' reputation accumulation can be carried out based on data utility, and a punishment mechanism is presented to reduce the waste of payment costs caused by malicious participants. Finally, we conduct an extensive study of our solution based on realistic data. Extensive experiments show that compared to the existing positive auction incentive mechanism (PAIM) and reverse auction incentive mechanism (RAIM), our proposed staged incentive mechanism (SIM) can effectively extend the incentive behavior from the recruiting stage to the sensing stage. It not only achieves being a real-time incentive in both the recruiting and sensing stages but also improves the utility of sensing data.

Inhibition of BRD4 Suppresses Cell Proliferation and Induces Apoptosis in Renal Cell Carcinoma.

BACKGROUND/AIMS: Renal cell carcinoma (RCC) remains an intractable genitourinary malignancy. Resistance to chemotherapy or targeted therapies in RCC is presumably due to the complicated underlying molecular mechanisms and insufficient understanding. The aim of this research was to assess the expression and role of bromodomain-4 protein (BRD4) in RCC and evaluate the effects of BRD4 inhibitor JQ1 for RCC treatment. METHODS: BRD4 expressionlevels were assessed by qRT-PCR and western blot in RCC tissues and cells. The effects of BRD4 knockdown or JQ1 on RCC cells were assessed by MTT assay and flow cytometry. The effects of in vivo treatment were evaluated through xenograft experiments. RESULTS: BRD4 is significantly overexpressed in RCC, and is related to tumor stage and lymph node metastasis. Inhibition of BRD4 suppressed RCC cell proliferation, induced cell apoptosis in vitro and repressed tumor growth in vivo. Inhibition of BRD4 decreased BCL2 and C-MYC expression while increased BAX and cleaved caspase3 expression, and strikingly diminished the recruitment of BRD4 to BCL2 promoter. CONCLUSIONS: Our research reveals that BRD4 probably play a critical role in RCC progression, and is a new promising target for pharmacological treatment directed against this intractable disease.