Background: Background parenchymal enhancement (BPE) is defined as the enhanced proportion of normal fibroglandular tissue on enhanced magnetic resonance imaging. BPE shows promise as a quantitative imaging biomarker (QIB). However, the lack of consensus among radiologists in their semi-quantitative grading of BPE limits its clinical utility. Methods: The main objective of this study was to develop a BPE quantification model according to clinical expertise, with the BPE integral being used as a QIB to incorporate both the volume and intensity of the enhancement metrics. The model was applied to 2,786 cases to compare our quantitative results with radiologists' semi-quantitative BPE grading to evaluate the effectiveness of using the BPE integral as a QIB for analyzing BPE. Comparisons between multiple groups of nonnormally distributed BPE integrals were performed using the Kruskal-Wallis test. Results: Our study found a considerable degree of concordance between our BPE quantitative integral and radiologists' semi-quantitative assessments. Specifically, our research results revealed significant variability in BPE integral attained through the BPE quantification framework among all semi-quantitative BPE grading groups labeled by experienced radiologists, including mild-moderate (P<0.001), mild-marked (P<0.001), and moderate-marked (P<0.001). Furthermore, there was an apparent correlation between BPE integral and BPE grades, with marked BPE displaying the highest BPE integral, followed by moderate BPE, with mild BPE exhibiting the lowest BPE integral value. Conclusions: The study developed and implemented a BPE quantification framework, which incorporated both the volume and intensity of enhancement and which could serve as a QIB for BPE.
Flexible sensors produced through three-dimensional (3D) printing have exhibited promising results in the context of underwater sensing detection (for applications in navigational vehicles and human activities). However, underwater vehicles and activities such as swimming and diving are highly susceptible to drag, which can cause negative impacts such as reduced speed and increased energy consumption. Additionally, microbial adhesion can shorten the service life of these vehicles. However, natural organisms are able to circumvent such problems, with shark skin offering excellent barrier properties and ruffled papillae providing effective protection against fouling. Here, we show that a sandwich system consisting of a spraying layer, conductive elastomer composite, and encapsulation layer can be printed for multifunctional integrated underwater sensors. The modulated viscoelastic properties of liquid metal form the foundation for printing features, while its pressure-activated properties offer the potential for switchable sensors. An integrated drag reduction and antifouling layer were created by combining the shark skin surface shield scale structure with the lotus leaf surface papillae structure. A 3D-printed flexible sensor was designed using our approach to monitor attitude changes and strain in underwater environments, showcasing its capabilities. Our printed sensors can reduce biological attachment density by more than 50% and reduce underwater drag by 8.6-10.3%.
Background and Objective: As a soft-tissue noninvasive ablation technology, high-intensity focused ultrasound (HIFU) has been widely used to treat many clinical diseases. However, traditional HIFU, based on thermal effects, has a high local working temperature, which may cause thermal damage to surrounding tissues and reduce the therapeutic effect. Based on the cavitation effect of HIFU, histotripsy can mechanically destroy the cells in the target lesion. This paper aims to explain the mechanism of histotripsy, summarize the research progress of animal models for clinical evaluation and clinical application, and analyze the advantages and limitations of histotripsy. Methods: Literature published from January 2006 to March 2022 was retrieved from the PubMed database. We reviewed these articles to examine histotripsy from the aspects of the mechanism, animal experiments, clinical trials, advantages, disadvantages, and optimization. Key Content and Findings: Histotripsy is a noninvasive, nonionizing, nonthermal ablation technique. The clinical application of histotripsy has made significant progress in the treatment of liver tumors, benign prostatic hyperplasia, and aortic valve calcification stenosis. Phase I clinical trials have demonstrated the safety and efficacy of histotripsy in the treatment of these diseases. More research is needed to evaluate and optimize its efficacy and safety and to fully explore its mechanism of action, pathological and immunological effects, and the short-term and long-term reactions of the body after treatment. Conclusions: Histotripsy has broad application prospects in ablation therapy and will benefit patients after more clinical trials are conducted in the future.
Background: Grading based on histopathologic indicators cannot accurately assess the prognosis of phyllodes tumor (PT) of the breast. This article aimed to investigate the correlation between PT prognosis and clinicopathological features, treatment, and surgical margin. Methods: The clinicopathological data of patients with pathologically confirmed PT at our institution were retrospectively collected. Univariate and multivariate Cox proportional risk models were employed to test the effects of different variables on the prognosis of PT. A nomogram to predict the 1-, 3-, 5-, and 10-year recurrence-free survival (RFS) of PT was proposed, and its discriminative ability and calibration were tested using the concordance index (C-index), area under the curve (AUC), and calibration plots. All statistical analyses were performed using R. Results: A total of 342 PT patients were included, including 242 benign (70.8%), 75 borderline (21.9%) and 25 malignant (7.3%) cases. The median follow-up period was 64.5 months (range, 3-179 months), 66 PT patients had local recurrence (LR), and four patients had distant metastasis. The 1-, 3-, 5-, and 10-year RFS of the PT patients were 90.8%, 81.8%, 78%, and 76.7%, respectively. Age, fibroadenoma (FA) surgery history, treatment, mitotic activity, and surgical margin were selected as the independent factors for PT prognosis. The nomogram showed good discriminative ability and calibration, as indicated by the C-index [0.78, 95% confidence interval (CI): 0.75-0.11]. Conclusions: Independent predictors related to PT prognosis were selected to establish a nomogram for predicting the RFS of PT. This nomogram was able to objectively stratify PT patients into prognostic groups and performed well in the internal validation.
Harmful algal blooms caused by Heterocapsa bohaiensis have broken out in aquaculture areas near Liaodong Bay, China, since 2012, resulting in mass mortality of Eriocheir sinensis larvae and substantial economic loss. Chlorella pyrenoidosa is a local phytoplankton species that is found in aquaculture ponds. However, the reason why H. bohaiensis dominated and proliferated in the phytoplankton community remains unknown. Previous studies have revealed the toxicity and hemolytic activity of H. bohaiensis. It is suspected that the out-competition of H. bohaiensis to C. pyrenoidosa was associated with toxicity. Filtrate and bi-algal cultures were investigated to determine the interspecific competition between H. bohaiensis and C. pyrenoidosa in this study. Filtrate experiments revealed that H. bohaiensis showed no toxin allelopathy in C. pyrenoidosa. However, the C. pyrenoidosa filtrates had significant allelopathic effects on the growth of H. bohaiensis. The bi-algal culture experiments and the simulation showed that the dominant species were dependent on the initial cell density ratios of the species and nutrient ratios. Therefore, H. bohaiensis achieved competitive advantage through exploitation competition but not allelopathy. The results contribute to the reasons for the occurrence of H. bohaiensis blooms in a further study.
Chlorella , Dinoflagellida , Harmful Algal Bloom , Phytoplankton , Ecology
Background: Due to differences in socioeconomic and cultural backgrounds, the characteristics and prognosis of Asian female patients choosing contralateral prophylactic mastectomy (CPM) are likely to be different from Western patients. To fill the research gap of CPM in Asian populations, this study aims to explore the application trend, survival benefits, decision-making factors, and satisfaction of CPM based on the Chinese patients undergoing CPM. Methods: The 0-III stage unilateral breast cancer (UBC) patients who received breast surgery in the Chinese PLA General Hospital from 2005 to 2017 were selected. The surgical procedures included simple mastectomy (SM), nipple-sparing mastectomy (NSM), breast conserving surgery (BCS), and CPM. Cox proportional regression analyses and Kaplan-Meier (KM) curve were performed to compare the overall survival (OS) and disease-free survival (DFS) rates between CPM group and unilateral mastectomy (UM) group. Proportional propensity score matching (PSM) with a 1:1 ratio was used to match the two groups and secondary survival analysis was performed. Logistic regression models were used to test predictive factors related to patients' CPM surgical decision-making. Results: Four thousand two hundred and seventy-six patients were included in the study, with 73 patients receiving CPM, 3,567 receiving SM, 151 receiving NSM, and 485 receiving BCS. CPM surgery was first used in 2007, with a peak application rate of 3.02% in 2016. Three thousand seven hundred and ninety-one patients were included in the survival analysis, with a median follow-up time of 66.60 months. Compared to UM patients, neither the KM survival curve nor Cox regression hazard analyses of CPM showed better OS (P=0.963; P=0.834). After PSM, CPM also did not exhibit significant survival benefits in OS (P=0.335) and DFS (P=0.409). The logistic regression analyses showed that NSM surgery and lower tumor-node-metastasis (TNM) stage were independent factors to promote the CPM decision-making of patients. The CPM group showed high overall satisfaction (84.9%) and relatively low appearance satisfaction (69.9%). Conclusions: CPM was practiced for the first time since 2007 in our hospital. CPM does not provide any OS and DFS benefits compared to UM and the appearance satisfaction procedure was relatively low. Therefore, clinicians should fully communicate with patients before surgery and be more cautious in giving CPM recommendations.
We previously developed chicken interleukin-1ß (IL-1ß) mutants as single-dose adjuvants that induce protective immunity when co-administered with an avian vaccine. However, livestock such as pigs may require a vaccine adjuvant delivery system that provides long-lasting protection to reduce the need for successive booster doses. Therefore, we developed chitosan-coated alginate microparticles as a carrier for bovine serum albumin (BSA) or porcine IL-1ß (pIL-1ß) and assessed their physical, chemical, and biological properties. Electrospraying of the BSA-loaded alginate microparticles (BSA/ALG MPs) resulted in an encapsulation efficiency of 50%, and those MPs were then coated with chitosan (BSA/ALG/CHI MPs). Optical and scanning electron microscopy, zeta potential analysis, and Fourier transform infrared spectroscopy were used to characterize these MPs. The BSA encapsulation parameters were applied to ALG/CHI MPs loaded with pIL-1ß, which were not cytotoxic to porcine fibroblasts but had enhanced bio-activity over unencapsulated pIL-1ß. The chitosan layer of the BSA/ALG/CHI MPs prevented burst release and facilitated sustained release of pIL-1ß for at least 28 days. In conclusion, BSA/ALG/CHI MPs prepared as a carrier for pIL-1ß may be used as an adjuvant for the formulation of pig vaccines.
Chitosan , Vaccines , Alginates/chemistry , Animals , Chitosan/chemistry , Glucuronic Acid/chemistry , Glucuronic Acid/pharmacology , Hexuronic Acids/chemistry , Hexuronic Acids/pharmacology , Interleukin-1beta , Serum Albumin, Bovine/chemistry , Swine
Background: Accurately predicting outcomes for patients with breast cancer receiving neoadjuvant chemotherapy (NAC) is critical for clinical decisions. Prognostic models applicable to the Chinese population remain limited. The Neo-Bioscore staging system has been utilized as a predictive model for survival of breast cancer patients after NAC. This study aimed to validate the applicability of Neo-Bioscore in a Chinese population and develop an improved staging system based on it to predict prognosis of Chinese patients more accurately. Methods: This study retrospectively collected clinicopathological and survival data in patients receiving NAC from February 2005 to August 2018 in PLA General Hospital. Discrimination, calibration and clinical usefulness were used to assess model performance. Univariate and multivariate analyses assessed relationships between clinicopathological factors and disease-specific survival. For model modification, postoperative pathological staging in the Neo-Bioscore was substituted with the posttreatment pathological tumor (ypT) stage and posttreatment pathological lymph node (ypN) stage. Neo-Bioscore and Modified Neo-Bioscore were compared with the American Joint Committee on Cancer (AJCC) staging system. Results: A total of 436 patients with a median follow-up of 67 months were included. Five-year disease-specific survival (DSS), overall survival, and disease-free survival rates were 88.0%, 87.9%, and 76.8%, respectively. The concordance index (C-index) of the Neo-Bioscore staging system, posttreatment pathological stage (PS), and pretreatment clinical stage (CS) for DSS were 0.78 [95% confidence interval (CI): 0.72-0.83], 0.75 (95% CI: 0.69-0.82), and 0.68 (95% CI: 0.62-0.74), respectively. No significant difference between the Neo-Bioscore and PS was observed in the C-index (P=0.399). ypT and ypN were included in Neo-Bioscore to replace PS and create a modified staging system named MNeo-Bioscore. The C-index for DSS of the MNeo-Bioscore was 0.82 (95% CI: 0.78-0.87), and the calibration curve and decision curve analysis (DCA) curve performed well in internal validation. Conclusions: The Neo-Bioscore staging system provided precise prognostic stratification for Chinese breast cancer patients receiving NAC; ypN and ypT stage may be substituted for PS to add significant prognostic value for Neo-Bioscore.
Background: Regardless of histological grade, phyllodes tumors (PTs) exhibit the potential of local recurrence. The National Comprehensive Cancer Network (NCCN) recommends wide local excision (WLE) with a 1 cm margin or more for borderline/malignant PTs but excisional biopsy for benign PTs. However, the treatment of benign PTs remains controversial and the clinicopathologic risk factors for the local recurrence is still unclear. Methods: We retrospectively analyzed 238 patients with PTs who underwent surgery at the Chinese PLA General Hospital from January 1, 2006 and April 30, 2020. We stratified our analysis according to histologic grade and explored the clinicopathologic factors to influence local recurrence (LR), including age, histologic grade, history of fibroadenoma, type of surgery [vacuum-assisted biopsy system (VABS), local excision (LE), wide local excision (WLE) and mastectomy]. Results: All 238 cases were categorized as benign (171, 71.8%), borderline (38, 16.0%), or malignant (29, 12.2%). The median follow-up was 50.2 months. In multivariate analysis, histologic grade (P<0.01) and history of fibroadenoma (P<0.01) were independent prognostic factors for LR. No difference existed in the recurrence rate of BPT treated with different surgical procedures (P=0.397), whereas a higher recurrence rate was found in VABS and LE subgroups than in WLE and mastectomy subgroups for borderline/malignant tumors (P<0.01). Conclusions: No association found between surgical modalities and LR rate for BPT. We suggested a "wait-and-watch" policy for patients with unexpected benign subtypes, instead of unnecessary re-excision. In addition, VABS or LE can be treated for BPT with small mass, whereas WLE or even mastectomy should be conducted for borderline/malignant PTs with large mass.
Background: Information is still controversial in the studies regarding the current optimal surgical management of phyllodes tumors (PTs) of the breast. Local recurrence (LR) may occur with an upgraded in the pathological grade, influencing the prognosis of patients with PT. This systematic review and meta-analysis aimed to investigate the association of LR risk with margin status and margin width which could have significant implications on the surgical management of PT. Methods: Independent and comprehensive searches were performed by two authors through five databases including PubMed, Medline, Embase, ScienceDirect and Cochrane Library from January 1990 to October 2021. Studies investigating the association between margin width, margin status and LR rates were considered for inclusion. Study quality was evaluated using the Newcastle-Ottawa Scale (NOS). Meta-analysis was performed using RevMan5.3 software, and statistical heterogeneity was assessed using the Chi-square test and quantified using the I2 statistic. Visual inspection of funnel plots was used to judge publication bias. Results: A total of 34 articles were included in this article, all of which with NOS scores above 5. Regardless of the PT grade, positive margin significantly increased the risk of LR [odds ratio (OR) 3.64, 95% confidence interval (CI): 2.60-5.12]. No significant difference was found in the risk of LR between the margins <1 and ≥1 cm (OR 1.39, 95% CI: 0.67-2.92). For benign and borderline PTs, there were no significant differences of the LR risk between breast-conserving surgery (BCS) and mastectomy (benign OR 0.68, 95% CI: 0.12-3.78; borderline OR 1.14, 95% CI: 0.29-4.51). While the LR risk was significantly increased by BCS for malignant PT (OR 2.77, 95% CI: 1.33-5.74). Discussion: Different surgical management strategies should be considered for different PT grades. BCS was a feasible option and margins <1 cm was not significantly associated with LR risk for all grade of PT. After BCS, benign PT with positive margin could adopt the "wait and watch" strategy with regular follow-up, while borderline and malignant PTs were expected to underwent re-excision to ensure negative margins. More studies are still needed to clarify and update the existing conclusions and improve the prognosis of PT patients.
In recent years, three PARP inhibitors and three CDK4/6 inhibitors have been approved by the FDA for the treatment of recurrent ovarian cancer and advanced ER-positive breast cancer, respectively. However, the clinical benefits of the PARPi or CDK4/6i monotherapy are not as satisfied as expected and benefit only a fraction of patients. Current studies have shown therapeutic synergy for combinations of PARPi and CDK4/6i in breast and ovarian cancers with homologous recombination (HR) proficiency, which represents a new synthetic lethal strategy for treatment of these cancers regardless HR status. Thus, any compounds or strategies that can combine PARP and CDK4/6 inhibition will likely have great potential in improving clinic outcomes and in benefiting more patients. In this study, we developed a novel compound, ZC-22, that effectively inhibited both PARP and CDK4/6. This dual-targeting compound significantly inhibited breast and ovarian cancer cells by inducing cell cycle arrest and severe DNA damage both in vitro and in vivo. Interestingly, the efficacy of ZC-22 is even higher than the combination of PARPi Olaparib and CDK4/6i Abemaciclib in most breast and ovarian cancer cells, suggesting that it may be an effective alternative for the PARPi and CDK4/6i combination therapy. Moreover, ZC-22 sensitized breast and ovarian cancer cells to cisplatin treatment, a widely used chemotherapeutic agent. Altogether, our study has demonstrated the potency of a novel CDK4/6 and PARP dual inhibitor, which can potentially be developed into a monotherapy or combinatorial therapy with cisplatin for breast and ovarian cancer patients with HR proficiency.
Antineoplastic Agents , Cyclin-Dependent Kinase 6/antagonists & inhibitors , Ovarian Neoplasms , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Carcinoma, Ovarian Epithelial/drug therapy , Cisplatin/pharmacology , Cisplatin/therapeutic use , Cyclin-Dependent Kinase 4 , Female , Humans , Neoplasm Recurrence, Local/drug therapy , Ovarian Neoplasms/pathology , Poly(ADP-ribose) Polymerase Inhibitors/pharmacology , Poly(ADP-ribose) Polymerase Inhibitors/therapeutic use
Tall cell carcinoma with reversed polarity (TCCRP) is an extremely rare type of invasive breast cancer with only 17 literatures and 75 cases reported. Knowledge on TCCRP is still scanty. The present study reported 2 cases of TCCRP, analyzed their clinicopathological characteristics, and used whole exome sequencing to perform genetic testing. Both two cases were proved to have typical clinicopathological manifestations (solid and papillary architectures lined by tall columnar cells with nuclei displaying "reverse polarization") and hotspot mutations (IDH2 and PIK3CA mutations) of TCCRP. Furthermore, positive expression of TTF-1 was found in a small number of tumor cells nuclei and normal ductal epithelial cells, while the negative rate of TTF-1 in previous case reports was 100%. Attention should be paid in core needle biopsy to avoid misdiagnosis. In addition, this article also reviewed all previous cases and demonstrated that the positive expression of calretinin might have an indicative significance for TCCRP, which could be used as one of the auxiliary diagnosis tools. The diagnosis of TCCRP requires comprehensive analysis of clinical pathology and genetic testing results. There is no clear treatment standard for TCCRP currently, further research should be reported to characterize and deeply investigate the diagnosis and treatment criteria of TCCRP.
OBJECTIVE: To provide a reference for clinical work and guide the decision-making of healthcare providers and end-users, we systematically reviewed the development, validation and classification of classical prognostic models for breast cancer. BACKGROUND: Patients suffering from breast cancer have different prognosis for its high heterogeneity. Accurate prognosis prediction and risk stratification for breast cancer are crucial for individualized treatment. There is a lack of systematic summary of breast cancer prognostic models. METHODS: We conducted a PubMed search with keywords "breast neoplasm", "prognostic model", "recurrence" and "metastasis", and screened the retrieved publications at three levels: title, abstract and full text. We identified the articles presented the development and/or validation of models based on clinicopathological factors, genomics, and machine learning (ML) methods to predict survival and/or benefits of adjuvant therapy in female breast cancer patients. CONCLUSIONS: Combining prognostic-related variables with long-term clinical outcomes, researchers have developed a series of prognostic models based on clinicopathological parameters, genomic assays, and medical figures. The discrimination, calibration, overall performance, and clinical usefulness were validated by internal and/or external verifications. Clinicopathological models integrated the clinical parameters, including tumor size, histological grade, lymph node status, hormone receptor status to provide prognostic information for patients and doctors. Gene-expression assays deeply revealed the molecular heterogeneity of breast cancer, some of which have been cited by AJCC and National Comprehensive Cancer Network (NCCN) guidelines. In addition, the models based on the ML methods provided more detailed information for prognosis prediction by increasing the data dimension. Combined models incorporating clinical variables and genomics information are still required to be developed as the focus of further researches.
BACKGROUND: Electrosurgical technology is widely used in surgical dissection and hemostasis, but the generated heat creates thermal injury to adjacent tissues and delays wound healing. The plasma blade (PB) applies pulsed radiofrequency (RF) to generate electrical plasma along the edge of a thin, flat, insulated electrode, minimizing collateral tissue damage. This study aimed to evaluate wound healing in swine skin following incision with a new surgical system that applies low-temperature plasma (NTS-100), a foreign PB, conventional electrosurgery (ES), and a scalpel blade. METHODS: In vitro porcine skin and an in vivo porcine skin model were used in this study. Full-thickness skin incisions 3 cm in length were made on the dorsum of each animal for each of the 5 surgical procedures at 0, 21, 28, 35, and 42 days. The timing of the surgical procedures allowed for wound-healing data points at 1, 2, 3, and 6 weeks accordingly. Local operating temperature and blood loss were quantified. Wounds were harvested at designated time points, tested for wound tensile strength, and examined histologically for scar formation and tissue damage. RESULTS: Local operating temperature was reduced significantly with NTS-100 (cut mode 83.12±23.55 °C; coagulation mode 90.07±10.6 °C) compared with PB (cut mode 94.46±11.48 °C; coagulation mode 100.23±6.58 °C, P<0.05) and ES (cut mode 208.99±34.33 °C, P<0.01; coagulation mode 233.37±28.69 °C, P<0.01) in vitro. Acute thermal damage from NTS-100 was significantly less than ES incisions (cut mode: 247.345±42.274 versus 495.295±103.525 µm, P<0.01; coagulation mode: 351.419±127.948 versus 584.516±31.708 µm, P<0.05). Bleeding, histological scoring of injury, and wound strength were equivalent for the NTS-100 and PB incisions. CONCLUSIONS: The local operating temperature of NTS-100 was lower than PB, and NTS-100 had similarly reliable safety and efficacy.
BACKGROUND: Breast ptosis is directly caused by Cooper's ligament laxity, with the decline of nipple areola complex (NAC) and mammary parenchyma. Breast cancer with ptosis is always a knotty problem that can hardly be repaired by classic breast conservation surgery (BCS) ending up with a pleasing appearance. We analyzed our 12 years' experience of performing inverted-T pattern techniques to treat bilateral breast ptosis, with or without breast cancer. METHODS: One hundred forty-eight breasts in 74 patients undergoing inverted-T pattern reduction mammoplasty were included in this study. Information about patients' clinical and surgical characteristics, complications, NAC sensitivity, cosmetic and oncological outcomes were collected and retrospectively analyzed. RESULTS: In the cohort of 57 patients with pure breast ptosis, the mean body mass index (BMI) was 25.2 kg/m2, and the mean weight of resected tissue from the left and right breast reductions were 744.9 and 756.7 g. In the cohort of 17 patients diagnosed as breast cancer with ptosis, the mean BMI was 25.1 kg/m2, and the mean weight of resected tissue were 504.1 g for left and 535.6 g for right side. The majority of repairs were performed for tumors located in the upper outer (58.8%), mostly with inferior or superomedial pedicles (90%). All the upper inner tumors were repaired with inferior pedicles. Minor complications such as seroma (8.1%), NAC epidermolysis (8.1%), delayed wound healing (4.1%) were detected postoperatively. Partial NAC necrosis occurred in one patient (1.4%). 82.4% of all the patients rated "very satisfied" or "satisfied" as the final cosmetic outcomes. NAC sensitivity was "very high" and "high" in 82.4% patients. No local occurrence, distant metastasis and mortality occurred in tumor patients. CONCLUSIONS: The inverted-T pattern reduction mammoplasty is a reliable technique to treat bilateral breast ptosis with a low complication rate. For cases with breast cancer, this technique can achieve both satisfying cosmetic outcomes and oncological safety.
Bleeding complications can cause significant morbidities and mortalities in both civilian and military conditions. The formation of stable blood clots or hemostasis is essential to prevent major blood loss and death from excessive bleeding. However, the body's self-coagulation process cannot accomplish timely hemostasis without the assistance of hemostatic agents under some conditions. In the past two decades, topical hemostatic materials and devices containing platelets, fibrin, and polysaccharides have been gradually developed and introduced to induce faster or more stable blood clot formation, updating or iterating traditional hemostatic materials. Despite the various forms and functions of topical hemostatic materials that have been developed for different clinical conditions, uncontrolled hemorrhage still causes over 30% of trauma deaths across the world. Therefore, it is important to fabricate fast, efficient, safe, and ready-to-use novel hemostatic materials. It is necessary to understand the coagulation process and the hemostatic mechanism of different materials to develop novel topical hemostatic agents, such as tissue adhesives and sealants from various natural and synthetic materials. This review discusses the structural features of topical hemostatic materials related to the stimulation of hemostasis, summarizes the commercially available products and their applications, and reviews the ongoing clinical trials and recent studies concerning the development of different hemostatic materials.
BACKGROUND: Triple-negative breast cancer (TNBC) is a malignant subtype of breast cancer, the main treatments for which are chemotherapy and surgery. PIK3CA is an oncogene that encodes the p110α subunit of class IA PI3K to regulate cell proliferation and apoptosis. Some reports have observed neoadjuvant chemotherapy (NAC) to have poor pathological complete response (pCR) rates in TNBC with PIK3CA mutation. This study aimed to explore the mechanism of how mutant PIK3CA alters chemotherapeutic susceptibility in TNBC. METHODS: TNBC cell lines (MDA-MB-231 and MDA-MB-468) with PIK3CA gene mutations (E545K and H1047R regions) and overexpression were established by transfection. NOD/SCID mice were used for in vivo experiments. Epirubicin was used as the chemotherapeutic agent. Cell viability, cell cycle, apoptosis, and Transwell assays were conducted for phenotype analysis. Western blot, quantitative reverse transcription-polymerase chain reaction, and immunohistochemistry were used to detect gene and protein expression levels. A clinical analysis of 50 patients with TNBC was also performed. RESULTS: Cell viability and Transwell assays showed that PIK3CA mutation promoted TNBC cell growth and conferred an enhanced migratory phenotype. Cell cycle and apoptosis assays showed that PIK3CA mutation moderately improved the proliferation ability of TNBC cells and remarkably inhibited their apoptosis. After epirubicin therapy, the proportion of early apoptotic cells decreased among cells with PIK3CA mutation. Further, xenograft tumors grew faster in NOD/SCID mice injected with mutated cell lines than in control group, suggesting that PIK3CA mutation caused chemotherapy resistance. Importantly, western blot and immunohistochemical analysis showed that cells and mouse tumors in the PIK3CA mutation groups exhibited different expression levels of apoptosis-related markers (Xiap, Bcl-2, and Caspase 3) and proteins associated with the PI3K/AKT/mTOR pathway (p110α, AKT, p-AKT, mTOR, p-mTOR, p-4E-BP1, p-p70S6K, and Pten). Moreover, prognostic analysis of 50 patients with TNBC indicated that PIK3CA mutation might be linked with relapse and death. CONCLUSIONS: PIK3CA mutation confers resistance to chemotherapy in TNBC by inhibiting apoptosis and activating the PI3K/AKT/mTOR signaling pathway.
