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Colorectal cancer (CRC) is a malignant tumor with a high incidence, ranking first among gastrointestinal malignancies. We investigated the impact of polyphyllin I (PPI), a natural compound found in Paris polyphylla, on CRC. PPI has been documented to exhibit anticancer activity against various tumors. This study aimed to assess the effects of PPI on colorectal cancer and explore its potential mechanisms. Our research demonstrated that PPI inhibited proliferation, promoted apoptosis, and induced G2 cell-cycle arrest in a dose-dependent manner. Additionally, our results indicated that PPI suppressed Notch signaling by downregulating the Notch1 receptor, its ligand Jagged1, and the downstream target Hes1 expression. Furthermore, we confirmed the antitumor effect of PPI on patient-derived organoids. In conclusion, our study indicates that PPI impedes the growth of colon cancer by suppressing the Notch signaling pathway.

With the rapid development of the field of life sciences, traditional 2D cell culture and animal models have long been unable to meet the urgent needs of modern biomedical research and new drug development. Establishing a new generation of experimental models and research models is of great significance for deeply understanding human health and disease processes, and developing effective treatment measures. As is well known, long research and development cycles, high risks, and high costs are the “three mountains” facing the development of new drugs today. Organoids and organ-on-chips technology can highly simulate and reproduce the human physiological environment and complex reactions in vitro, greatly improving the accuracy of drug clinical efficacy prediction, reducing drug development costs, and avoiding the defects of drug testing animal models. Therefore, organ-on-chips have enormous potential in medical diagnosis and treatment.

PurposeWe prospectively analyzed the correlation between fasting plasma glucose (FPG) and the risk of breast cancer in women; explored the independent risk factors for breast cancer in women, and compared the effect of FPG level on the risk of young and non-young breast cancer. Our study provides new evidence and ideas for research into breast cancer etiology in China, improves the accuracy of secondary prevention of breast cancer, and provides options for the clinical diagnosis and treatment of breast cancer patients with diabetes.Materials and methodsThree cohorts of women participating in the first health examination of the Kailuan Group in 2006, 2008 and 2010 were assembled to conduct a descriptive analysis of the baseline data on FPG. The cumulative incidence of breast cancer in different groups over 13 years was calculated using the Kaplan-Meier method and groups were compared using the log-rank test. A Cox proportional hazards regression model was used to analyze the association between FPG level and the risk of breast cancer.ResultsThe cumulative incidence of breast cancer increased in people with FPG higher than 5.29 mmol/L, but there was no significant difference in the effect of different levels of FPG on the risk of young breast cancer in the population. Different degrees of fasting glucose can affect the risk of non-young breast cancer in the population.ConclusionThe results of this study suggest that the risk of breast cancer can be reversed by early intervention to control levels of FPG. Regular monitoring of FPG may reduce the misdiagnosis rate of breast cancer in the population.

Abstract Enabling materials to undergo reversible dynamic transformations akin to the behaviors of living organisms represents a critical challenge in the field of material assembly. The pursuit of such capabilities using conventional materials has largely been met with limited success. Herein, the discovery of reversible constrained dissociation and reconfiguration in MXene films, offering an effective solution to overcome this obstacle is reported. Specifically, MXene films permit rapid intercalation of water molecules between their distinctive layers, resulting in a significant expansion and exhibiting confined dissociation within constrained spaces. Meanwhile, the process of capillary compression driven by water evaporation reinstates the dissociated MXene film to its original compact state. Further, the adhesive properties emerging from the confined disassociation of MXene films can spontaneously induce fusion between separate films. Utilizing this attribute, complex structures of MXene films can be effortlessly foamed and interlayer porosity precisely controlled, using only water as the inducer. Additionally, a parallel phenomenon has been identified in graphene oxide films. This work not only provides fresh insights into the microscopic mechanisms of 2D materials such as MXene but also paves a transformative path for their macroscopic assembly applications in the future.

PurposeThis study aimed to investigate the factors associated with pathologic node-negativity (ypN0) in patients who received neoadjuvant chemotherapy (NAC) to develop and validate an accurate prediction nomogram.MethodsThe CSBrS-012 study (2010–2020) included female patients with primary breast cancer treated with NAC followed by breast and axillary surgery in 20 hospitals across China. In the present study, 7,711 eligible patients were included, comprising 6,428 patients in the primary cohort from 15 hospitals and 1,283 patients in the external validation cohort from five hospitals. The hospitals were randomly assigned. The primary cohort was randomized at a 3:1 ratio and divided into a training set and an internal validation set. Univariate and multivariate logistic regression analyses were performed on the training set, after which a nomogram was constructed and validated both internally and externally.ResultsIn total, 3,560 patients (46.2%) achieved ypN0, and 1,558 patients (20.3%) achieved pathologic complete response in the breast (bpCR). A nomogram was constructed based on the clinical nodal stage before NAC (cN), ER, PR, HER2, Ki67, NAC treatment cycle, and bpCR, which were independently associated with ypN0. The area under the receiver operating characteristic curve (AUC) for the training set was 0.80. The internal and external validation demonstrated good discrimination, with AUCs of 0.79 and 0.76, respectively.ConclusionWe present a real-world study based on nationwide large-sample data that can be used to effectively screen for ypN0 to provide better advice for the management of residual axillary disease in breast cancer patients undergoing NAC.

Background: There is an interest in performing de-escalating axillary surgery after neoadjuvant chemotherapy (NAC). However, the significance of residual axillary node disease after NAC has not been well studied. Objectives: To investigate the pathological residual axillary lymph node tumor burden (ypN) of patients with initial clinical nodal stage cN0-1 breast cancer after NAC and determine its prognostic value. Design: Initial cN0-1 breast cancer patients who received NAC followed by axillary surgery at the First Hospital of Jilin University and the First Affiliated Hospital of Xi’an Jiaotong University between January 2011 and December 2019 were included. Methods: Survival outcomes were compared according to different clinical and pathological stage and nodal response to NAC. The main outcomes were disease-free survival (DFS) and overall survival (OS). Factors associated with survival were defined by Cox regression analysis. Results: A total of 911 patients were included, among whom 260 had cN0 and 651 had cN1 tumors. After NAC, 410 patients were ypN0, and another 501 were ypN+. The median follow-up time was 63 months. There was no significant difference in DFS or OS between the cN0 and cN1 groups in hormone receptor positive (HR+)/human epidermal growth factor receptor 2 positive (HER2+) and HR−/HER2− subtypes; instead, ypN status was significantly related to DFS and OS. In HR+/HER2− subtype, both cN and ypN stages did not show significant survival differences, but the ypN number and the nodal response to NAC showed significant prognostic value ( p

Abstract. In this study, we aimed to explore the safety and vaccination coverage data of Chinese patients with breast cancer receiving coronavirus disease 2019 (COVID-19) vaccination. The patients were recruited from 41 hospitals across 20 Chinese provinces. The vaccination coverage was approximately 22.4%, and the frequency of total adverse events was 13.3% after the first dose and 9.9% after the second dose. The most frequent adverse reaction within 14 days of the first dose was local pain (5.7%). Unvaccinated patients were very likely to reject the vaccine rather than be hesitant in patients with old age (odds ratio [OR], 1.238; 95% confidence interval [CI], 1.101–1.391), chronic disease history (OR, 1.189; 95% CI, 1.057–1.337), and cancer relapse (OR, 1.398; 95% CI, 1.233–1.585). Of the unvaccinated patients with breast cancer, 54.1% opted to receive COVID-19 vaccines if more data were available. Considering the safety but low vaccination coverage for breast cancer, increased positive attitudes and acceptance toward COVID-19 vaccines are important.

Aim:This study aims to identify suitable candidates for axillary sentinel lymph node biopsy (SLNB) or targeted axillary dissection (TAD) among clinical N2 (cN2) triple-negative (TN) or HER2 positive (HER2+）breast cancer patients following neoadjuvant therapy（NAT）.Background: Despite the substantial axillary burden in cN2 breast cancer patients, high pathological response rates can be achieved with NAT in TN or HER2+ subtypes, thus enabling potential downstaging of axillary surgery.Methods: A retrospective analysis was conducted on data from the CSBrS-012 study, screening 709 patients with initial cN2, either HER2+ or TN subtype, from January 1, 2010 to December 31, 2020. The correlation between axillary pathologic complete response (pCR) (yPN0) and breast pCR was examined.Results: Among the 177 cN2 patients who achieved breast pCR through NAT, 138 (78.0 %) also achieved axillary pCR. However, in the 532 initial clinical N2 patients who did not achieve breast pCR, residual axillary lymph node metastasis persisted in 77.4 % (412/532) of cases. The relative risk of residual axillary lymph node metastasis in patients who did not achieve breast pCR was 12.4 (8.1–19.1), compared to those who did achieve breast pCR, P

BackgroundThe widespread use of vaccines against the novel coronavirus disease (COVID-19) has become one of the most effective means to establish a population immune barrier. Patients with cancer are vulnerable to COVID-19 infection, adverse events, and high mortality, and should be the focus of epidemic prevention and treatment. However, real-world data on the safety of vaccines for patients with breast cancer are still scarce. ObjectiveThis study aims to compare the safety of COVID-19 vaccines between patients vaccinated before or after being diagnosed with breast cancer. MethodsPatients with breast cancer who sought medical advice from October 2021 to December 2021 were screened. Those who received COVID-19 vaccines were enrolled in this study to analyze the safety of the vaccines. The primary outcome was patient-reported adverse events (AEs). All events after vaccine injection were retrospectively documented from the patients. ResultsA total of 15,455 patients with breast cancer from 41 hospitals in 20 provinces in China were screened, and 5766 patients who received COVID-19 vaccines were enrolled. Of those enrolled, 45.1% (n=2599) of patients received vaccines before breast cancer diagnosis, 41.3% (n=2379) were vaccinated after diagnosis, and 13.6% (n=784) did not known the accurate date of vaccination or cancer diagnosis. Among the patients vaccinated after diagnosis, 85.4% (n=2032) were vaccinated 1 year after cancer diagnosis and 95.4% (n=2270) were vaccinated during early-stage cancer. Of all 5766 vaccinated patients, 93.9% (n=5415) received an inactivated vaccine, 3.7% (n=213) received a recombinant subunit vaccine, and 2.4% (n=138) received other vaccines, including adenovirus and mRNA vaccines. In the first injection of vaccines, 24.4% (n=10, 95% CI 11.2-37.5) of patients who received an adenovirus vaccine reported AEs, compared to only 12.5% (n=677, 95% CI 11.6-13.4) of those who received an inactivated vaccine. Patients with metastatic breast cancer reported the highest incidence of AEs (n=18, 16.5%, 95% CI 9.5-23.5). Following the second injection, patients who received an inactivated vaccine (n=464, 8.7%, 95% CI 8.0-9.5) and those who received a recombinant vaccine (n=25, 8.7%, 95% CI 5.5-12.0) reported the same incidence of AEs. No significant differences in patient-reported AEs were found between the healthy population and patients with breast cancer (16.4% vs 16.9%, respectively); the most common AEs were local pain (11.1% vs 9.1%, respectively), fatigue (5.5% vs 6.3%, respectively), and muscle soreness (2.3% vs 3.6%, respectively). The type of vaccine and time window of vaccination had little impact on patient-reported AEs. ConclusionsCompared with patients vaccinated before breast cancer diagnosis, there were no significant differences in patient-reported AEs in the patients vaccinated after diagnosis. Thus, it is safe for patients with breast cancer, especially for those in the early stage, to receive COVID-19 vaccines. Trial RegistrationChinese Clinical Trial Registry ChiCTR2200055509; https://tinyurl.com/33zzj882

Long-chain n-3 polyunsaturated fatty acid (PUFA) supplementation has shown potential benefits in the prevention of coronary heart disease (CHD); however, the impact of omega-3 fatty acid levels on CHD risk remains a subject of debate. Here, we aimed to investigate the association between n-3 PUFA levels and the risk of CHD, with particular reference to the subtypes of n-3 PUFA. Methods: Prospective studies and retrospective case-control studies analyzing n-3 PUFA levels in CHD, published up to 30 July 2022, were selected. A random effects meta-analysis was used for pooled assessment, with relative risks (RRs) expressed as 95% confidence intervals (CIs) and standardized mean differences expressed as weight mean differences (WMDs). Subgroup and meta-regression analyses were conducted to assess the impact of n-3 PUFA exposure interval on the CHD subtype variables of the study. Results: We included 20 prospective studies (cohort and nested case-control) and 16 retrospective case-control studies, in which n-3 PUFAs were measured. Higher levels of n-3 PUFAs (ALA, EPA, DPA, DHA, EPA + DHA, total n-3 PUFAs) were associated with a reduced risk of CHD, with RRs (95% CI) of 0.89 (0.81, 0.98), 0.83 (0.72, 0.96); 0.80 (0.67,0.95), 0.75 (0.64, 0.87), 0.83 (0.73, 0.95), and 0.80 (0.70, 0.93), respectively, p < 0.05. CHD patients had significantly lower n-3 PUFA levels compared to healthy controls (p < 0.05). In the subgroup analysis, a significant inverse trend was found for both fatal CHD and non-fatal CHD with n-3 PUFA (EPA + DHA) levels. Also, the link between n-3 PUFA levels in erythrocytes with total CHD was generally stronger than other lipid pools. Conclusions: n-3 PUFAs are significantly related to CHD risk, and these findings support the beneficial effects of n-3 PUFAs on CHD.

Context Cardamonin (CDN) can suppress cell growth in colorectal cancer (CRC), a common digestive malignancy.Objective We explored the effect and mechanism of CDN on metastatic CRC.Materials and methods Two cell lines (HT29 and HCT116) were initially treated with CDN at different concentrations (5, 10 and 20 μmol/L) or 50 μmol/L propranolol (positive control) for 24 or 48 h. Then, the two cell lines were separately transfected with siADRB2 and ADRB2 overexpression plasmids, and further treated with 10 μmol/L CDN for 24 h. The cell viability, migration and invasion were determined by cell counting kit-8 (CCK-8), wound healing and transwell assays, respectively. The levels of ADRB2, matrix metalloprotease (MMP)-2, MMP-9, E-cadherin and N-cadherin were measured by Western blotting or/and RT-qPCR. A CRC metastasis model was established to evaluate the antimetastatic potential of CDN (25 mg/kg).Results ADRB2 (3.2-fold change; p

Abstract Background Recently, an increasing number of studies have been conducted on circular RNAs (circRNAs) that have demonstrated their different roles in a variety of biological processes. Moreover, a large number of circRNAs have been shown to be involved in the occurrence and development of breast cancer (BC). Main body Both functional and mechanistic experiments have shown that circular RNAs (circRNAs) can act as competing endogenous RNAs by sponging miRNAs, encoding proteins, and regulating parental genes. In doing so, circRNAs modulate the proliferation, migration, apoptosis, and invasion of BC cells in vitro as well as tumor growth and metastasis in vivo. Moreover, scores of circRNAs have been demonstrated to be related to clinicopathological features, prognosis, and treatment sensitivity in patients with BC; many circRNAs have shown potential as biomarkers for diagnosis, drug sensitivity, and prognosis prediction. Furthermore, researchers have focused on circRNAs as potential therapeutic targets. Conclusion In this review, we briefly summarize the functions and categories of circRNAs, their different roles in BC, and recent research and therapeutic progress related to circRNAs.

This paper investigates the problem of real-time parameter identification for ship maneuvering parameters and wave peak frequency in an ocean environment. Based on the idea of Euler discretion, a combined model of ship maneuvering and wave peak frequency (ship–wave) is made a discretion, and a discrete-time auto-regressive moving-average model with exogenous input (ARMAX) is derived for parameter identification. Based on the ideas of stochastic gradient identification and multi-innovation theory, a multi-innovation stochastic gradient (MI-SG) algorithm is derived for parameter identification of the ship–wave discretion model. Maximum likelihood theory is introduced to propose a maximum likelihood-based multi-innovation stochastic gradient (ML-MI-SG) algorithm. Compared to the MI-SG algorithm, the ML-MI-SG algorithm shows improvements in both parameter identification accuracy and identification convergence speed. Simulation results verify the effectiveness of the proposed algorithm.

BackgroundThe axillary lymph node positive (ypN+) rate in patients with clinically node-negative (cN0) breast cancer who have achieved breast pathologic complete response (bpCR) after neoadjuvant systemic therapy (NST) is extremely low, and this population has the potential to be exempt from sentinel lymph node biopsy (SLNB). However, an overview of the ypN+ rate in this population for different breast cancer subtypes is lacking.ObjectiveTo provide the pooled ypN+ rate in cN0 patients who achieved bpCR after NST in different breast cancer subtypes defined by hormone receptor (HR) status and human epidermal growth factor receptor 2 (HER2) status.MethodsA systematic literature search was conducted in Embase and PubMed on July 20, 2022. Two authors independently selected studies that met the inclusion criteria and extracted all data. The pooled ypN+ rates for each subtype were calculated by a random-effects model using the Stata 16.0 metaprop command.ResultsThe pooled analysis of 9609 cN0 patients who achieved bpCR showed that the ypN+ rate was lowest for the HR+/HER2+ (0%) subtype, followed by HR+/HER2- (5.1%), HR-/HER2+ (0.6%), and HR-/HER2- (0.3%). Additionally, 6571 cT1-T2N0 patients who achieved bpCR had a pooled ypN+ rate of 0.6%, and the ypN+ rates for different subtypes were as follows: HR+/HER2+ (1.7%), HR+/HER2- (2.7%), HR-/HER2+ (0.1%), and HR-/HER2- (0.8%).ConclusionOur results suggested that cN0 patients who achieve bpCR may be exempt from axillary surgery in the HR+/HER2-, HR+/HER2+, and HR-/HER2- subtypes because of the extremely low probability of residual axillary lymph node disease. However, the safety of omitting axillary surgery needs to be further confirmed by prospective studies.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/#recordDetails, identifier CRD42022351739.

Using STAT3 inhibitors as a potential strategy in cancer therapy have attracted much attention. Recently, celastrol has been reported that it could directly bind to and suppress the activity of STAT3 in the cardiac dysfunction model. To explore more effective STAT3 inhibiting anti-tumour drug candidates, we synthesised a series of celastrol derivatives and biologically evaluated them with several human cancer cell lines. The western blotting analysis showed that compound 4 m, the most active derivative, could suppress the STAT3’s phosphorylation as well as its downstream genes. SPR analysis, molecular docking and dynamics simulations’ results indicated that the 4m could bind with STAT3 protein more tightly than celastrol. Then we found that the 4m could block cell-cycle and induce apoptosis on HCT-116 cells. Furthermore, the anti-tumour effect of 4m was verified on colorectal cancer organoid. This is the first research that discovered effective STAT3 inhibitors as potent anti-tumour agents from celastrol derivatives.

Background: In the era of targeted therapy, whether patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer are exempted from anthracycline usage in the neoadjuvant setting is controversial. Objectives: Our objective was to retrospectively analyze the differences in pathological complete remission (pCR) rates between the anthracycline group and the nonanthracycline group. Design: The CSBrS-012 study (2010–2020) included female primary breast cancer patients with neoadjuvant chemotherapy (NAC) who underwent standard breast and axillary surgery post-NAC. Methods: A logistic proportional hazard model was applied to estimate the association of covariates with pCR. Propensity score matching (PSM) was performed to balance the differences in baseline characteristics, and subgroup analyses were performed using the Cochran–Mantel–Haenszel test. Results: A total of 2507 patients were enrolled: the anthracycline group ( n = 1581, 63%) and the nonanthracycline group ( n = 926, 37%). A pCR was recorded in 17.1% (271/1581) of patients in the anthracycline group and in 29.3% (271/926) in the nonanthracycline group, and the difference in the pCR rate between the two groups was statistically significant [odds ratio (OR) = 2.00, 95% confidence interval (CI) (1.65–2.43); p

Background and objectivesThe relationship between age and the outcome of breast cancer neoadjuvant chemotherapy (NAC) remains controversial, and little is known about the choice of surgical treatment for young patients. In this multicenter real-world study, we sought to analyze the outcome of NAC as well as the current status and trend of surgical decision-making after NAC in young breast cancer patients.MethodsThe medical records of patients from 20 hospitals in different regions of China were collected retrospectively. The study population included females diagnosed with cT1-4N0-3M0 breast cancer who received NAC from January 2010 to December 2020.ResultsA total of 9,643 eligible patients were included, 1,945 (20.2%) of whom were ≤40 years old. Young patients tend to have a higher tumor stage and a higher proportion of Luminal B and triple-negative breast cancer (TNBC) tumors compared with the >40-year-old group. The breast pathological complete response (pCR) rate in the young group was 20.3%, and Luminal B tumor was more likely to obtain pCR in young patients. The implementation rate of breast-conserving surgery (BCS) and breast reconstruction surgery was higher in young patients and tended to increase over time. In different regions of China, there were great differences in the choice of surgical treatment after NAC among young patients.ConclusionBreast cancer in young women has unique clinical characteristics, but age does not affect the overall pCR rate. In China, the BCS rate after NAC is increasing over time but is still at a low level.

Liquiritin is a natural flavone with a variety of pharmacological effects derived from the medicinal food homology plant Glycyrrhiza uralensis Fisch. As a kind of lethal allergic reactions, pseudo-allergic reactions (PARs) arise from the Mas-related G protein coupled receptor X2 (MRGPRX2)-triggered fast degranulation of mast cells (MCs). In the current work, the anti-pseudo-allergy action and potential mechanisms of liquiritin were explored in vivo and in vitro. Liquiritin suppressed the calcium influx and degranulation elicited by Compound 48/80 (C48/80) in mouse peritoneal mast cells (MPMCs). In mice, liquiritin also inhibited the C48/80-elicited hind paw extravasation, as well as the elevations in TNF-α and histamine levels. Molecular docking combined with detection of HEK293T cells expressing human MRGPRX2 showed that liquiritin was a potential MRGPRX2 antagonist and inhibited PARs through the PI3K/AKT and PLCγ signaling pathways downstream of MRGPRX2. The present work opens a new avenue for the PARs management.

In this study, celastrol (CEL) microbial transformation was performed by Streptomyces olivaceus CICC 23628 for the first time. Two new friedelanes derivatives (CEL-1 and CEL-2) as metabolites were isolated, and their structures were elucidated based on the NMR and HR-MS analysis. Then we investigated their anti-proliferation activities in three human cancer cell lines (A549, HCT-116, HepG2) in vitro. Mechanistic studies showed that CEL-2 could induce cell apoptosis and block cell-cycle on HCT-116 cells. The western blotting analysis showed that CEL-2 could suppress the STAT3′s phosphorylation as well as its downstream genes. Furthermore, SPR analysis revealed that CEL-2 could direct bind with STAT3 protein. These studies suggest that the derivative CEL-2 may exert an anti-colorectal cancer effect via inhibiting STAT3, thereby inducing apoptosis and blocking cell-cycle. Finally, we further verified the anti-tumor effect of CEL-2 on the colorectal cancer organoid model. Our researches suggest that the biotransformation of celastrol is a potential approach to discovering new STAT3 inhibitors as anti-tumor agent.

This paper focuses on the fixed-time leader–follower formation control of multiple underwater vehicles (MUVs) in the presence of external disturbances. First, an adaptive fixed-time disturbance observer (AFxDO) is developed to deal with unknown time-varying environmental disturbances. The developed AFxDO guarantees the fixed-time convergence property of the disturbance observation error and no prior information on the external disturbances or their derivatives is required. Then, with the aid of the developed AFxDO, a distributed event-triggered fixed-time backstepping controller was developed to achieve the leader–follower formation tracking control of MUVs. To solve the “explosion of complexity” problem inherent in the conventional backstepping, a nonlinear filter is introduced to obtain the derivative of the virtual control law. Furthermore, to reduce the communication burden, the event-triggered mechanism is integrated into the formation tracking controller. The stability analysis shows that the closed-loop MUV system is practical fixed-time stable. Finally, simulation results demonstrate the effectiveness of the proposed scheme.

Abstract Background Anterior resection syndrome (ARS) is characterized by the diverse and interchangeable evacuatory symptoms that may occur following distal colorectal resection. We aimed to investigate the effect and potential mechanisms of ozone perfusion on rats with anterior rectal resection (ARR). Material and methods After establishment of rat ARR model, 20, 40 and 80 ug/ml ozone was used to treat rats by enema administration. The pathological examination of intestinal tissue was detected using hematoxylin–eosin staining. The rate of loose stools, minimum threshold volume of abdominal withdrawal reflex (AWR) and Bristol grade were used to evaluate the degree of abnormal defecation function. Subsequently, the levels of oxidative stress- and inflammation-related markers, 5-hydroxytryptamine (5-HT), inducible nitric oxide synthase (iNOS) and nitric oxide (NO) in the serum and intestinal tissue were determined with the corresponding kits. Meanwhile, the expression of nuclear factor kappa B (NF-κB) p65, transient receptor potential vanilloid (TRPV)1, TRPV4, iNOS and 5-HT receptor 3A (5-HTR3A) was determined with RT-qPCR and western blotting. Results Ozone administration (20 and 40 ug/ml) significantly alleviated the pathological changes of intestinal tissue-induced by ARR, accompanied by the decreased loose stools rate, Bristol score and increased abdominal withdraw reflex. However, 80 ug/ml of ozone intervention played opposite roles in the aforementioned changes with 20 and 40 ug/ml of ozone. Additionally, remarkably elevated reactive oxygen species (ROS), malonaldehyde (MDA), superoxide dismutase (SOD), 5-HT, iNOS and NO levels were observed in the ozone-treated groups (20 and 40 ug/ml), while high dose of ozone drastically improved ROS, MDA, 5-HT, iNOS and NO levels but reduced the activity of SOD. Consistently, the contents of inflammatory factors were decreased after low and middle doses of ozone administration. However, high dose of ozone aggravated the inflammatory injury. Moreover, 20 and 40 ug/ml ozone upregulated TRPV1 and TRPV4 expression but downregulated 5-HTR3A expression, which was restored after 80 ug/ml of ozone intervention. Remarkably, the levels of NF-κB p65 and iNOS were dose-dependently enhanced following ozone treatment. Conclusions Taken together, low concentration of ozone attenuated intestinal injury induced by ARR via balancing oxidative stress and inflammation, but high concentration of ozone exacerbated the intestinal injury, which might be related to the 5-HT and TRPV signaling.

Abstract Lubrication failure is one of the main failure forms of gear failure. Time varying meshing stiffness is an important factor affecting the dynamic behavior of gears. However, the influence of oil film stiffness is usually ignored in the research process. In this paper, according to the meshing characteristics of double involute gears, based on the non-Newtonian thermal EHL theory, a new calculation method of normal and tangential oil film stiffness for double involute gears is established by the idea of subsection method. The oil film stiffness difference between double involute gears and common involute gears is analyzed, and the influence of tooth waist order parameters, working conditions, and thermal effect on the oil film stiffness are studied. The results reveal that there are some differences between normal and tangential oil film stiffness between double involute gears and common involute gears, but there is little difference. Compared with the torque, rotation speed and initial viscosity of the lubricating oil, the tooth waist order parameters have less influence on the oil film stiffness. Thermal effect has a certain influence on normal and tangential oil film stiffness, which indicates that the influence of thermal effect on the oil film can not be ignored. This research proposes a calculation method of normal and tangential oil film stiffness suitable for double involute gears, which provides a theoretical basis for improving the stability of the transmission.

BackgroundMitoxantrone hydrochloride injection for tracing (MHI), a new strategy to identify lymph nodes, has not been tested for axillary node staging in breast cancer. This multicenter, self-controlled, non-inferiority trial aimed to evaluate MHI’s efficacy and safety in sentinel lymph node biopsy (SLNB).MethodsThe trial was conducted across seven hospitals from December 2019 to December 2020. Patients with early-stage breast cancer received MHI and technetium-99m (99mTc) during the surgery. Sentinel node detection rates were compared between MHI and 99mTc to evaluate non-inferiority and concordance. Non-inferiority was valid if the lower limit of the 95% CI of sentinel node relative detection rate difference was ≥−5%.ResultsSLN relative detection rate of MHI was 97.31% (362/372). Of the SLNs, 79.69% (871/1093) were co-detected by both tracers. Of the patients, 4.13% (16/387) had adverse events and recovered during the follow-up.ConclusionsMHI is a lymphatic tracer with comparable efficacy to radionuclides and can be used alone or in combination with radioactive substances for SLNB.Clinical Trial Registrationhttp://www.chinadrugtrials.org.cn, CTR20192435.

Breast cancer is now the most common cancer worldwide, and it is also the main cause of cancer-related death in women. Survival rates for female breast cancer have significantly improved due to early diagnosis and better treatment. Nevertheless, for patients with advanced or metastatic breast cancer, the survival rate is still low, reflecting a need for the development of new therapies. Mechanistic insights into metastatic breast cancer have provided excellent opportunities for developing novel therapeutic strategies. Although high-throughput approaches have identified several therapeutic targets in metastatic disease, some subtypes such as triple-negative breast cancer do not yet have an apparent tumor-specific receptor or pathway to target. Therefore, exploring new druggable targets in metastatic disease is a high clinical priority. In this review, we summarize the emerging intrinsic therapeutic targets for metastatic breast cancer, including cyclin D-dependent kinases CDK4 and CDK6, the PI3K/AKT/mTOR pathway, the insulin/IGF1R pathway, the EGFR/HER family, the JAK/STAT pathway, poly(ADP-ribose) polymerases (PARP), TROP-2, Src kinases, histone modification enzymes, activated growth factor receptors, androgen receptors, breast cancer stem cells, matrix metalloproteinases, and immune checkpoint proteins. We also review the latest development in breast cancer immunotherapy. Drugs that target these molecules/pathways are either already FDA-approved or currently being tested in clinical trials.

Abstract The present study aimed to investigate the efficacy and toxicity of pegylated liposomal doxorubicin (PLD) in preoperative neoadjuvant chemotherapy for patients with breast cancer by comparing with conventional anthracycline. This study is a non-randomized controlled trial. Prospective analysis was conducted after matching as required. A total of 146 patients with confirmed diagnosis of breast cancer by histopathological examinations were enrolled into the observation group and control group in 1:1 ratio. Each of the cases in the observation group was required to correspond to another in the control group according to the requirements including age, molecular subtype, axillary node status, and regimen of the preoperative neoadjuvant chemotherapy. The chemotherapy was based on regimens consisting of anthracyclines, paclitaxel or docetaxel, and/or platinum. PLD was used at least twice in the observation group, with traditional anthracycline as a contrast in the control group. Clinical responses as well as cardiac side effects and other adverse reactions were evaluated by clinical and imaging examinations such as electrocardiogram (ECG) and color Doppler ultrasound during the chemotherapy. Pathologic examinations were performed following the surgeries after preoperative neoadjuvant chemotherapy. All the patients in both groups completed the preoperative neoadjuvant chemotherapy according to their original regimens. The postoperative pathological evaluation revealed a higher pathologic complete response (PCR) rate and significantly more patients of grade V of the Miller-Payne grading system in the observation group as compared to the control group (p = 0.047). In addition, the observation group recorded an evidently lower occurrence of the adverse cardiac events (p = 0.014), ECG changes (p = 0.048), and the relatively severe adverse reactions such as myelosuppression. Compared with conventional anthracycline drugs, PLD has a better pathologic response and safety performance, as well as a similar clinical effectiveness in preoperative neoadjuvant chemotherapy for breast cancer.

BackgroundLeptin (LEP) plays a physiological role through its specific receptor (LEPR) and is involved in the occurrence and development of breast cancer. Our current study aimed at determining the influence of single-nucleotide polymorphisms (SNPs) in the genes coding for LEP and LEPR on breast cancer risk.MethodsIn the present study, 963 breast cancer cases and 953 controls were enrolled. Five SNPs of LEP and two of LEPR were chosen to evaluate the correlation of selected SNPs with breast cancer susceptibility among women in northern and eastern China. Analyses were further stratified by body mass index (BMI), waist–hip rate (WHR), estrogen receptor, and progesterone receptor status. The expression patterns of risk variant-associated genes were detected by expression quantitative trait locus (eQTL) analysis with eQTLGen and The Cancer Genome Atlas database.ResultsThere were significant differences between breast cancer cases and control groups in the menopausal status and family history of breast cancer. Two SNPs (rs1137101 and rs4655555) of the LEPR gene decreased overall breast cancer risk, and other five SNPs showed no significant association with breast cancer risk. rs1137101 (GA vs. GG; adjusted OR = 0.719, 95% CI = 0.578–0.894, p = 0.003) and rs4655555 (TT vs. AA; adjusted OR = 0.574, 95% CI = 0.377–0.873, p = 0.009) significantly decreased breast cancer risk after Bonferroni correction for multiple testing. In subgroup analyses, the GA and GA + AA genotypes of LEPR rs1137101 associated with decreased breast cancer risk in the subgroup of BMI ≤ 24 kg/m2 or WHR ≥ 0.85 after Bonferroni correction. Furthermore, we found that the expressions of rs4655555-associated gene LEPR and leptin receptor overlapping transcript (LEPROT) were upregulated in breast cancer tumor tissues compared with adjacent normal tissues, and a higher expression of LEPR in tumor tissues was correlated with poor prognosis of breast cancer patients using The Cancer Genome Atlas Breast Invasive Carcinoma (TCGA-BRCA) data.ConclusionOur study demonstrated that the polymorphisms rs1137101 and rs4655555 located in the LEPR gene decreased breast cancer risk in Chinese females, which might be a research-worthy bio-diagnostic marker and applied for early prediction and risk assessment of breast cancer.

Compared with traditional oral and injection administration, the transdermal administration of traditional Chinese medicine has distinctive characteristics and advantages, which can avoid the “first pass effect” of the liver and the destruction of the gastrointestinal tract, maintain a stable blood concentration, and prolong drug action time. However, the basic theory and technology research in transdermal drug delivery are relatively limited at present, especially regarding research on new carriers of transdermal drug delivery and pharmacokinetic studies of the skin, which has become a bottleneck of transdermal drug delivery development. Triptolide is one of the main active components of Tripterygium wilfordii, which displays activities against mouse models of polycystic kidney disease and pancreatic cancer but its physical properties and severe toxicity limit its therapeutic potential. Due to the previously mentioned advantages of transdermal administration, in this study, we performed a detail analysis of the pharmacokinetics of a new transdermal triptolide delivery system. Triptolide nanoemulsion gels were prepared and served as new delivery systems, and the ex vivo characteristics were described. The metabolic characteristics of the different triptolide transdermal drug delivery formulations were investigated via skin–blood synchronous microdialysis combined with LC/MS. A multiscale modeling framework, molecular dynamics and finite element modeling were adopted to simulate the transport process of triptolide in the skin and to explore the pharmacokinetics and mathematical patterns. This study shows that the three−layer model can be used for transdermal drug delivery system drug diffusion research. Therefore, it is profitable for transdermal drug delivery system design and the optimization of the dosage form. Based on the drug concentration of the in vivo microdialysis measurement technology, the diffusion coefficient of drugs in the skin can be more accurately measured, and the numerical results can be verified. Therefore, the microdialysis technique combined with mathematical modeling provides a very good platform for the further study of transdermal delivery systems. This research will provide a new technology and method for the study of the pharmacokinetics of traditional Chinese medicine transdermal drug delivery. It has important theoretical and practical significance in clarifying the metabolic transformation of percutaneous drug absorption and screening for appropriate drugs and dosage forms of transdermal drug delivery.

BackgroundColorectal cancer (CRC) is one of the most common malignant gastrointestinal cancers in the world with a 5-year survival rate of approximately 68%. Although researchers accumulated many scientific studies, its pathogenesis remains unclear yet. Detecting and removing these malignant polyps promptly is the most effective method in CRC prevention. Therefore, the analysis and disposal of malignant polyps is conducive to preventing CRC.MethodsIn the study, metabolic profiling as well as diagnostic biomarkers for CRC was investigated using untargeted GC-MS-based metabolomics methods to explore the intervention approaches. In order to better characterize the variations of tissue and serum metabolic profiles, orthogonal partial least-square discriminant analysis was carried out to further identify significant features. The key differences in tR–m/z pairs were screened by the S-plot and VIP value from OPLS-DA. Identified potential biomarkers were leading in the KEGG in finding interactions, which show the relationships among these signal pathways.ResultsFinally, 17 tissue and 13 serum candidate ions were selected based on their corresponding retention time, p-value, m/z, and VIP value. Simultaneously, the most influential pathways contributing to CRC were inositol phosphate metabolism, primary bile acid biosynthesis, phosphatidylinositol signaling system, and linoleic acid metabolism.ConclusionsThe preliminary results suggest that the GC-MS-based method coupled with the pattern recognition method and understanding these cancer-specific alterations could make it possible to detect CRC early and aid in the development of additional treatments for the disease, leading to improvements in CRC patients’ quality of life.

Objective To determine whether aldehyde dehydrogenase 1 (ALDH1) immunostaining in axillary lymph node metastases in patients with breast cancer is associated with poor clinical prognosis. Methods This retrospective study reviewed data from the medical records of patients with immunohistochemistry-confirmed invasive ductal carcinoma (IDC) and 1–3 metastatic lymph nodes in the ipsilateral axilla between December 2012 and July 2015. The association between ALDH1 immunostaining in axillary lymph node metastases and clinical parameters and prognosis was analysed using χ 2 -test, Kaplan–Meier survival analysis, univariate and multivariate Cox regression analyses. Results A total of 229 patients with IDC were enrolled in the study. The median follow-up was 61 months (range, 20–89 months). Patients with ALDH1-positive axillary lymph node metastases had significantly shorter relapse-free survival and overall survival compared with those with ALDH1-negative axillary lymph node metastases. ALDH1 immunostaining in axillary lymph node metastases was a significant predictor of poor prognosis in univariate and multivariate analyses. Conclusion This large study with long-term follow-up suggests that ALDH1 immunostaining in axillary lymph node metastases is an independent predictor of poor prognosis in patients with breast cancer. The clinical relevance of this finding should be confirmed in further well-designed prospective studies.

Although chemotherapy can improve the overall survival and prognosis of cancer patients, chemoresistance remains an obstacle due to the diversity, heterogeneity, and adaptability to environmental alters in clinic. To determine more possibilities for cancer therapy, recent studies have begun to explore changes in the metabolism, especially glycolysis. The Warburg effect is a hallmark of cancer that refers to the preference of cancer cells to metabolize glucose anaerobically rather than aerobically, even under normoxia, which contributes to chemoresistance. However, the association between glycolysis and chemoresistance and molecular mechanisms of glycolysis-induced chemoresistance remains unclear. This review describes the mechanism of glycolysis-induced chemoresistance from the aspects of glycolysis process, signaling pathways, tumor microenvironment, and their interactions. The understanding of how glycolysis induces chemoresistance may provide new molecular targets and concepts for cancer therapy.

Energy density, which is an important indicator of the performance of solid propellants, is known to increase with the addition of 2,4,6,8,10,12-hexanitro-2,4,6,8,10,12-hexaazaisowurtzitane (CL-20). However, it remains unclear how CL-20 affects the decomposition of ammonium perchlorate (AP) and energy release. Here, the effects of CL-20 on the combustion performance and agglomeration of propellants were investigated. The addition of CL-20 decreased AP decomposition temperature and the energy required for the transformation of AP crystals from orthorhombic to cubic. The burning rate and pressure exponent of the propellant with 42% CL-20 were significantly higher than those of the propellant containing 20% CL-20. Thus, adding CL-20 to the propellant improves the energy characteristics and burning rate and the pressure exponent increases. At low combustion chamber pressure, the agglomeration of the propellant containing a high content of CL-20 will be blown away from the combustion surface only after staying on that surface for a short time. In this process, the probability of volume growth of the agglomeration after merging with other agglomerations greatly decreases, thus reducing the overall agglomerate particle sizes; further, the addition of a small amount of CL-20 to the propellant may lead to a reduction in agglomerate particle sizes. AP with a smaller particle size weakens the agglomeration in the combustion process and decreases the number of agglomerates with large particle sizes. These findings lay the foundation for the development of novel high-energy propellants.

Neoadjuvant chemotherapy (NAC) has become the main treatment option for breast cancer. Its adverse drug reactions (ADRs) make NAC painful both physiologically and psychologically. The factor pathological complete remission (pCR) describes how well a series of six or more chemotherapeutic treatments works on a patient. This study investigated the possibility of predicting pCR using only the nodal sizes of the first three treatments. A best feature combination for each breast cancer subtype was screened from the real nodal sizes of the first three treatments and the nodal sizes` of the next three treatments predicted from those of the first three ones. The prediction was evaluated by the metrics Avc = (sensitivity + specificity)/2. A triple-negative breast cancer (TN) patient may have an estimation of pCR Avc = 0.8696 after taking just three treatments. At least Avc = 0.7594 was achieved for all the four breast cancer subtypes investigated in this study.

ObjectiveAxillary node status after neoadjuvant chemotherapy (NCT) in early breast cancer patients influences the axillary surgical staging procedure. This study was conducted for the identification of the likelihood of patients being node pathological complete response (pCR) post NCT. We aimed to recognize patients most likely to benefit from sentinel lymph node biopsy (SLNB) following NCT and to reduce the risk of missed detection of positive lymph nodes through the construction and validation of a clinical preoperative scoring prediction model.MethodsThe existing data (from March 2010 to December 2018) of the Chinese Society of Clinical Oncology Breast Cancer Database (CSCO-BC) was used to evaluate the independent related factors of node pCR after NCT by Binary Logistic Regression analysis. A predictive model was established according to the score of considerable factors to identify ypN0. Model performance was confirmed in a cohort of NCT patients treated between January 2019 and December 2019 in Henan Cancer Hospital, and model discrimination was evaluated via assessing the area under the receiver operating characteristic (ROC) curve (AUC).ResultsMultivariate regression analysis showed that the node stage before chemotherapy, the expression level of Ki-67, biologic subtype, and breast pCR were all independent related factors of ypN0 after chemotherapy. According to the transformation and summation of odds ratio (OR) values of each variable, the scoring system model was constructed with a total score of 1–5. The AUC for the ROC curves was 0.715 and 0.770 for the training and the validation set accordingly.ConclusionsA model was established and verified for predicting ypN0 after chemotherapy in newly diagnosed cN+ patients and the model had good accuracy and efficacy. The underlined effective model can suggest axillary surgical planning, and reduce the risk of missing positive lymph nodes by SLNB after NCT. It has great value for identifying initial cN+ patients who are more appropriate for SLNB post-chemotherapy.

This study was to assess the prognosis stratification of the clinical-pathologic staging system incorporating estrogen receptor (ER)-negative disease, the nuclear grade 3 tumor pathology (CPS + EG), Neo-Bioscore, and a modified Neo-Bioscore system in breast cancer patients after preoperative systemic therapy (PST). A retrospective multicenter cohort study was conducted from 12 participating hospitals’ databases from 2006 to 2015. Five-year disease free survival (DFS), disease specific survival (DSS), and overall survival (OS) were calculated using Kaplan–Meier Method. Area under the curve (AUC) of the three staging systems was compared. Wald test and maximum likelihood estimates in Cox proportional hazards model were used for multivariate analysis. A total of 1,077 patients were enrolled. The CPS + EG, Neo-Bioscore, and modified Neo-Bioscore could all stratify the DFS, DSS, and OS (all P < 0.001). While in the same stratum of Neo-Bioscore scores 2 and 3, the HER2-positive patients without trastuzumab therapy had much poorer DSS (P = 0.013 and P values < 0.01, respectively) as compared to HER2-positive patients with trastuzumab therapy and HER2-negative patients. Only the modified Neo-Bioscore had a significantly higher stratification of 5-year DSS than PS (AUC 0.79 vs. 0.65, P = 0.03). So, the modified Neo-Bioscore could circumvent the limitation of CPS + EG or Neo-Bioscore.Clinical Trial RegistrationClinicalTrials.gov, identifier NCT03437837.

Breast cancer (BC) is the most common gynecologic tumor worldwide where aberrant expression of microRNAs (miRNAs) is frequently involved. Here, we evaluated the function of miR-375 on BC development and the molecules implicated. Differentially expressed genes between tumor and paired normal tissues from BC patients were screened out by microarray analyses. miR-375 was abundantly expressed in BC tissues and cells, and it was correlated with the poor prognosis of patients. Downregulation of miR-375 was introduced into BC cell lines MCF-7 and HCC1954, after which the viability, colony formation, migration, and invasion were suppressed, while the apoptosis of cells was increased, and the xenograft tumors in nude mice were reduced as well. EZH2 increased methylation and phosphorylation of signal transducer and activator of transcription 3 (STAT3) and increased transcription activity of miR-375, while miR-375 directly targeted FOXO1. Either overexpression of EZH2 or downregulation of FOXO1 blocked the functions of anti-miR-375 in cells and animals. FOXO1 was found as an activator of the p53 signaling pathway. This study showed that miR-375 is an important oncogene in BC. EZH2 is an upstream regulator of miR-375 through mediating the methylation of STAT3, while FOXO1 is a downstream target mRNA of miR-375 that activates the p53 signaling pathway to suppress BC development.

The construction of abundant pore channels between the layers of Ti3C2Tx MXene film is an important approach to fully exploit the 2D macromolecular properties of MXene (Ti3C2Tx), which is of great significance for further realizing the practical application of MXene macroscopic assemblies in the field of electromagnetic interference shielding and capacitive storage. However, there is still a lack of systematic introductions and prospects of this field, thus far. In this review, starting from the preparation of MXene macroscopic assemblies, the 3D porous MXene films, constructed by sacrificial templating, vapor foaming, and light foaming, as well as their corresponding properties of electromagnetic interference shielding and capacitive storage, are introduced. In addition, the current bottlenecks and great challenges of 3D porous MXene films are deeply analyzed, and effective solutions for future application development trends are proposed.

Objective: To investigate the association between metabolic syndrome and breast cancer and to elucidate the potential mechanism underlying this association.Patients and Methods: Based on baseline data drawn from 21 hospitals in 11 provinces of China, we performed a case–control study among 1,127 women (595 cases and 532 controls), divided into premenopausal, and postmenopausal subgroups. Student's t test, Pearson's χ2 test, and logistic regression analyses were performed to ascertain the association between breast cancer and metabolic syndrome, including all of its components. In addition, we attempted to clarify the potential role of adiponectin in this association.Results: Among the components of metabolic syndrome, abnormal waist circumference was the component that markedly increased breast cancer risk in premenopausal women (OR 1.447, 95% CI 1.043–2.006). Metabolic syndrome with clusters of special risk factors showed an association with breast cancer risk. Among all these components of metabolic syndrome, the hypertriglyceridemic-waist (HW) phenotype significantly increased breast cancer risk (OR 1.56, 95% CI 1.02–2.39), regardless of menopausal status, rendering it a strong predictor of breast cancer. Total adiponectin levels and high-molecular-weight adiponectin were reversely associated with metabolic syndrome. In addition, total adiponectin levels among breast cancer patients were much lower than among controls (p = 0.005) only in the HW phenotype subgroup. Furthermore, the HW phenotype was associated with increased risk of estrogen receptor/progesterone receptor-positive (ER+/PR+) breast cancer, with a 95% (OR = 1.95, 95% CI:1.21–3.13) increase. However, there was no significant association between the HW phenotype and both ER+/PR– and ER–/PR– subtypes. These results suggested that low adiponectin levels may be a mechanism that explains the association between the HW phenotype and breast cancer risk.Conclusion: Metabolic syndrome with special cluster factors is related to breast cancer risk; in particular, the HW phenotype can be regarded as a strong predictor of breast cancer. As an important factor involved in fat metabolism, adiponectin may strongly predict metabolic syndrome, especially the HW phenotype and breast cancer. Further research into this mechanism and epidemiological studies are needed. This study provides new evidence for the role of a healthy lifestyle in preventing breast cancer.

Abstract Backgrounds Tamoxifen is typically used to treat patients with estrogen receptor alpha (ERα)-positive breast cancer. However, 30% of these patients gain acquired resistance to tamoxifen during or after tamoxifen treatment. As a Ras modulator, Nogo-B receptor (NgBR) is required for tumorigenesis through the signaling crosstalk with epidermal growth factor (EGF) receptor (EGFR)-mediated pathways. NgBR is highly expressed in many types of cancer cells and regulates the sensitivity of hepatocellular carcinoma to chemotherapy. In this study, we found the expression of NgBR is increased in tamoxifen-resistant ERα-positive breast cancer cells. Methods Tamoxifen-resistant ERα-positive MCF-7 and T47D breast cancer cell lines were established by culturing with gradually increased concentration of 4-hydroxytamoxifen (4-OHT). The effects of NgBR on tamoxifen resistance was determined by depleting NgBR in these cell lines using previously validated small interfering RNA (siRNA). The effects of 4-OHT on cell viability and apoptosis were determined using well-accepted methods such as clonogenic survival assay and Annexin V/propidium iodide staining. The alteration of EGF-stimulated signaling and gene expression was determined by western blot analysis and real-time PCR, respectively. Results NgBR knockdown with siRNA attenuates EGF-induced phosphorylation of ERα and restores the sensitivity to tamoxifen in ERα-positive breast cancer cells. Mechanistically, our data demonstrated that NgBR knockdown increases the protein levels of p53 and decreases survivin, which is an apoptosis inhibitor. Conclusions These results suggested that NgBR is a potential therapeutic target for increasing the sensitivity of ERα-positive breast cancer to tamoxifen.

Objective: Axillary lymph node dissection (ALND) may be unnecessary in 20%–60% of breast cancer patients with sentinel lymph node (NSLN) metastasis. The aim of the present study was to review the medical records of Chinese patients with early-stage breast cancer and positive NSLN metastasis to identify clinicopathological characteristics as risk factors for non-NSLN metastasis.Methods: The medical records of 2008 early-stage breast cancer patients who received intraoperative sentinel lymph node biopsy (SLNB) between 2006 and 2016 were retrospectively reviewed. These patients were clinically and radiologically lymph node-negative and had no prior history of receiving neoadjuvant chemotherapy or endocrinotherapy. The clinicopathological characteristics of patients with positive NSLN metastasis who underwent ALND were investigated.Results: In the present study, 296 patients with positive NSLN metastases underwent ALND. Positive non-NSLN metastases were confirmed in 95 patients (32.1%). On univariate analysis, ≥ 3 positive NSLN metastases (P P = 0.023), and lymphovascular invasion (P = 0.04) were associated with non-NSLN metastasis (P Conclusions: The number of positive NSLNs, NSLN macrometastases, and lymphovascular invasion were correlated with non-SLN metastasis. The number of positive SLNs was an independent predictor for non-NSLN metastasis. When 2 or 3 risk factors were present in one patient, the probability of non-NSLN was higher than that in the American College of Surgeons Oncology Group Z0011 trial (27.3%); thus, avoiding ALND should be considered carefully.

Abstract The prognostic value of routine laboratory variables in breast cancer has been largely overlooked. Based on laboratory tests commonly performed in clinical practice, we aimed to develop a new model to predict disease free survival (DFS) after surgical removal of primary breast cancer. In a cohort of 1,596 breast cancer patients, we analyzed the associations of 33 laboratory variables with patient DFS. Based on 3 significant laboratory variables (hemoglobin, alkaline phosphatase, and international normalized ratio), together with important demographic and clinical variables, we developed a prognostic model, achieving the area under the curve of 0.79. We categorized patients into 3 risk groups according to the prognostic index developed from the final model. Compared with the patients in the low-risk group, those in the medium- and high-risk group had a significantly increased risk of recurrence with a hazard ratio (HR) of 1.75 (95% confidence interval [CI] 1.30–2.38) and 4.66 (95% CI 3.54–6.14), respectively. The results from the training set were validated in the testing set. Overall, our prognostic model incorporating readily available routine laboratory tests is powerful in identifying breast cancer patients who are at high risk of recurrence. Further study is warranted to validate its clinical application.

Abstract Background Colon cancer, one of the most common causes of cancer-related deaths, arises from adenomatous polyps. In these years, circulating microRNAs (miRNAs) have attracted increasing attention as novel biomarkers for colon cancers. The dysregulated circulating miRNAs in patients with colon adenomas has not been well-understood. Methods Here, we aimed to identify miRNA profile in the serum of patients with colon adenomas or colon cancer by using microarray. Then we validated eight differentially expressed miRNAs (DEMs) by qRT-PCR and predicted their targets. Results We identified 26 DEMs from Adenomas versus Normal comparison (11 up-regulations and 15 down-regulations), 72 DEMs from Cancer versus Normal comparison (19 up-regulations and 53 down-regulations) and 17 DEMs from Cancer versus Adenomas comparison (4 up-regulations and 13 down-regulations). Moreover, three DEMs identified from Cancer versus Normal comparison were included in the list of DEMs identified from Cancer versus Adenomas comparison, and may be specific diagnostic biomarkers for colon cancer. Five down-regulated miRNAs identified from Cancer versus Normal comparison were included in the list of DEMs identified from Adenomas versus Normal comparison, and may be important for the development of colon polyps and cancer. Conclusions We discovered 8 circulating miRNAs associated with colon adenomas and colon cancer, and these miRNAs may potentially serve as noninvasive screening biomarkers for colon cancer. Our study is useful for expanding our understanding in the development of colon adenomas and colon cancer, and thus provide novel insights into colon cancer pathogenesis and prevention.

MAPKAPK2 (MK2), the direct substrate of p38 MAPK, has been well-acknowledged as an attractive drug target for cancer therapy. However, few studies have assessed the functions of it in multiple myeloma (MM). In the present study, MK2 expression of MM patients was analyzed by gene expression profiling (GEP) and array-based comparative genomic hybridization (aCGH). Several experiments in vitro including MTT assay, Western blot and flow cytometry analysis were performed to identify the function of MK2 in MM. In addition, we conducted mouse survival experiments to explain the effects of MK2 on MM in vivo. mRNA level of MK2 and chromosomal gain of MK2 locus in MM cells significantly increased compared to normal samples. Furthermore, MM patients with high expression of MK2 were associated with a poor outcome. Follow-up studies showed that MK2 exerted a remarkably positive effect on MM cell proliferation and drug-resistance. Further exploration focusing on MK2 inhibitor IV revealed its inhibitory action on MM growth and drug-resistance, as well as improving survival in mouse models. In addition, a combination of MK2 inhibitor IV and the key MM therapeutic agents including bortezomib, doxorubicin, or dexamethasone facilitated curative effects on inhibiting MM cell proliferation. Taken together, our study reveals the clinical relevance of MK2 inhibition in MM and demonstrates that targeting MK2 may afford a new therapeutic approach to MM.

Abstract Background Breast cancer is the most common cancer among women worldwide. Here, we report the prevalence of BRCA1/2 mutations in patients with high‐risk breast cancer from Inner Mongolia and Jilin, China, which was a part of a nationwide project on the detection of BRCA1/2 mutations in Chinese patients with hereditary breast cancer. Methods According to the criteria, index patients from a total of 245 independent families were initially recruited. All 49 exons of BRCA1 and BRCA2 and adjacent noncoding regions were screened for mutations based on next‐generation sequencing from collected saliva. Results We detected 17 BRCA1/2 variants in 18 of 216 (8.3%) index patients with high‐risk breast cancer. Among these, seven mutations were novel, including four BRCA1 mutations (c.123_124delCAinsAT, c.5093_5096delCTAA, c.5396‐2A>G, and c.2054delinsGAAGAGTAACAAGTAAGAAGAGTAACAAGAAG), and three BRCA2 mutations (c.304A>T, c.7552_7553insT, and c.9548_9549insA). The BRCA1/2 variants were identified in 14% (8/57) of the patients with triple‐negative breast cancer and in 6.3% (10/159) of the patients with non‐triple‐negative breast cancer. There was no significant difference between the two groups (p = 0.07). A higher frequency for BRCA1 mutations was observed in patients with triple‐negative breast cancer than in those with non‐triple‐negative breast cancer (12.3% vs. 2.5%, p = 0.004). The frequencies of the BRCA2 mutations were not significantly different between patients with triple‐negative breast cancer and those with non‐triple‐negative breast cancer (1.8% vs. 3.8%, p = 0.46). Conclusion We found that patients with triple‐negative breast cancer had a higher frequency of BRCA1 mutations than those with non‐triple‐negative breast cancer. In this study, no significant associations between the BRCA1/2 mutation status and age, family history of breast cancer, ovarian cancer, pancreatic cancer and prostate cancer, number of primary lesions, tumor size, or lymph node metastasis were observed.

Raman spectroscopy has been widely used as an important clinical tool for real-time in vivo cancer diagnosis. Raman information can be obtained from whole organisms and tissues, at the cellular level and at the biomolecular level. The aim of this paper is to review the newest developments of Raman spectroscopy in the field of breast cancer diagnosis and treatment. Raman spectroscopy can distinguish malignant tissues from noncancerous/normal tissues and can assess tumor margins or sentinel lymph nodes during an operation. At the cellular level, Raman spectra can be used to monitor the intracellular processes occurring in blood circulation. At the biomolecular level, surface-enhanced Raman spectroscopy techniques may help detect the biomarker on the tumor surface as well as evaluate the efficacy of anticancer drugs. Furthermore, Raman images reveal an inhomogeneous distribution of different compounds, especially proteins, lipids, microcalcifications, and their metabolic products, in cancerous breast tissues. Information about these compounds may further our understanding of the mechanisms of breast cancer.