A nomogram for predicting pathologic node negativity after neoadjuvant chemotherapy in breast cancer patients: a nationwide, multicenter retrospective cohort study (CSBrS-012).

Purpose: This 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. Methods: The 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. Results: In 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. Conclusion: We 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.

Implantation of Adipose-Derived Mesenchymal Stromal Cells (ADSCs)-Lining Prosthetic Graft Promotes Vascular Regeneration in Monkeys and Pigs.

BACKGROUND: Current replacement procedures for stenosis or occluded arteries using prosthetic grafts have serious limitations in clinical applications, particularly, endothelialization of the luminal surface is a long-standing unresolved problem. METHOD: We produced a cell-based hybrid vascular graft using a bioink engulfing adipose-derived mesenchymal stromal cells (ADSCs) and a 3D bioprinting process lining the ADSCs on the luminal surface of GORE-Tex grafts. The hybrid graft was implanted as an interposition conduit to replace a 3-cm-long segment of the infrarenal abdominal aorta in Rhesus monkeys. RESULTS: Complete endothelium layer and smooth muscle layer were fully developed within 21 days post-implantation, along with normalized collagen deposition and crosslinking in the regenerated vasculature in all monkeys. The regenerated blood vessels showed normal functionality for the longest observation of more than 1650 days. The same procedure was also conducted in miniature pigs for the interposition replacement of a 10-cm-long right iliac artery and showed the same long-term effective and safe outcome. CONCLUSION: This cell-based vascular graft is ready to undergo clinical trials for human patients.

Solanine induces ferroptosis in colorectal cancer cells through ALOX12B/ADCY4 molecular axis.

OBJECTIVES: Colorectal cancer (CRC) is the fourth most commonly diagnosed cancer worldwide. Solanine is a phytochemical extracted from traditional Chinese medicine with widely reported anticancer effects. Here, we investigated the potential role of solanine in regulating ferroptosis in CRC cells and scrutinized the molecular mechanism. METHODS: Cell growth and cytotoxicity were examined using CCK-8 proliferation assay and lactate dehydrogenase assay. Oxidative stress was determined by measuring glutathione (GSH), malondialdehyde, and reactive oxygen species (ROS) levels. Subcellular changes in mitochondria were examined by transmission electron microscopy. Gene and protein expression levels were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Protein-protein interaction was determined by co-immunoprecipitation. KEY FINDINGS: Solanine arrested cell proliferation in CRC cells and induced typical ferroptotic changes. Solanine treatment promoted ROS production, lipid peroxidation, and cell membrane disruption, while the cellular level of antioxidant GSH was reduced upon solanine treatment. ALOX12B was identified as a molecular mediator of solanine to promote ferroptosis. Solanine treatment upregulated ALOX12B levels and silencing ALOX12B could suppress solanine-induced ferroptosis. Further, ADCY4 was found to physically associate with ALOX12B and maintain ALOX12B protein stability. Silencing ADCY4 destabilized ALOX12B and attenuated solanine-induced ferroptosis. CONCLUSIONS: Our data demonstrated the ferroptosis-inducing effect of solanine in CRC cells, and revealed ALOX12B/ADCY4 molecular axis as the ferroptosis mediator of solanine. Solanine may synergize with existing ferroptosis inducer as an anticancer strategy in CRC, which warrants further validation in animal experiments.

Predictive factors that influence the clinical efficacy of umbilical cord-derived mesenchymal stromal cells in the treatment of type 2 diabetes mellitus.

BACKGROUND: Our previous single-center, randomized, double-blinded, placebo-controlled phase 2 study evaluated the safety and effectiveness of human umbilical cord mesenchymal stromal cell (UC-MSC) transfusion for treating patients with type 2 diabetes mellitus (T2DM). Indeed, this potential treatment strategy was able to reduce insulin use by half in a considerable number of patients. However, many other patients' responses to UC-MSC transfusion were insignificant. The selection of patients who might benefit from UC-MSC treatment is crucial from a clinical standpoint. METHODS: In this post hoc analysis, 37 patients who received UC-MSC transfusions were divided into two groups based on whether their glycated hemoglobin (hemoglobin A1c, or HbA1c) level was less than 7% after receiving UC-MSC treatment. The baseline differences between the two groups were summarized, and potential factors influencing efficacy of UC-MSCs for T2DM were analyzed by univariate and multivariate logistic regression. The correlations between the relevant hormone levels and the treatment effect were further analyzed. RESULTS: At the 9-week follow-up, 59.5% of patients achieved their targeted HbA1c level. Male patients with lower baseline HbA1c and greater C-peptide area under the curve (AUCC-pep) values responded favorably to UC-MSC transfusion, according to multivariate analysis. The effectiveness of UC-MSCs transfusion was predicted by AUCC-pep (cutoff value: 14.22 ng/h/mL). Further investigation revealed that AUCC-pep was increased in male patients with greater baseline testosterone levels. CONCLUSIONS: Male patients with T2DM with greater AUCC-pep may be more likely to respond clinically to UC-MSC therapy, and further large-scale multi-ethnic clinical studies should be performed to confirm the conclusion.

In vitro effect of Er: YAG laser irradiation in caries cavity preparation on biobehaviors of adjacent human dental pulp cells in the pulp chamber.

The erbium-doped yttrium aluminum garnet (Er: YAG) laser has been successfully applied in caries removal; however, little is known about proper parameters of Er: YAG laser on different conditions of caries removal, especially the influence of Er: YAG irradiation on human dental pulp cells (hDPCs). Here, we tested the effects of Er: YAG laser at different output energy levels (100, 200, 300, 400, and 500 mJ) on biobehaviors of hDPCs. To simulate clinical deep caries conditions, hDPCs were cultured on the pulpal side of 500-µm-thick dentin disks in an in vitro pulp chamber model. Temperature change, structural change, and ablation depth of dentin disk were also recorded. The findings suggested that the biological behaviors of hDPCs are strongly correlated with the energy output of the Er: YAG laser. Er: YAG laser irradiation at 100 mJ may be proper and safe for deep caries removal since it would not cause any adverse effect on hDPCs biobehaviors.

Knowledge on cause, clinical manifestation and treatment for fibromyalgia among medical doctors: A worldwide survey.

OBJECTIVES: Hench introduced the fibromyalgia syndrome almost 50 years ago. In the meantime, the prevalence has increased, the clinical criteria have changed and the way we explain (chronic) pain has altered. DESIGN: In the current study, we conducted a worldwide survey in which we investigate whether medical doctors are familiar with the American College of Rheumatology (ACR) criteria for fibromyalgia and, if so, whether these medical doctors adhere to the clinical guidelines following evidence-based treatments. RESULTS: In total, 286 medical doctors from 43 countries spread over 6 continents filled out the survey. In most of the countries, the diagnosis fibromyalgia was used. Only 10% adhere to the ACR criteria, widespread pain (44%), unrefreshed sleep (24%), fatigue (20%) and cognitive problems (8%) were most used diagnostic criteria. Of the respondents, 94 (32%) mentioned that the cause is unknown or idiopathic, but also a wide variety of other causes was mentioned. More than 70 different treatment options were provided, of which 24% of the responses were classified as according to the clinical guidelines. From this study, we conclude that many medical doctors do not follow the ACR criteria; the majority has an inappropriate knowledge of causes for fibromyalgia and that a minority of treatment advice adhere to the guidelines.

What Are the Long-term Outcomes of Locking Plates for Nonosteoporotic Three-part and Four-part Proximal Humeral Fractures With a Minimum 10-year Follow-up Period?

BACKGROUND: Proximal humeral fractures (PHFs) often occur in elderly individuals who experience low-energy falls. Open reduction and internal fixation (ORIF) of the proximal humerus is typically performed in young, active patients because of their good bone quality and high functional demands. Although good short-term results have been reported after ORIF in young patients, few studies have specifically evaluated long-term outcomes. QUESTIONS/PURPOSES: (1) What are the long-term clinical outcomes scores and (2) radiologic outcomes of nonosteoporotic three-part and four-part PHFs treated with locking plates? (3) What complications occurred after treatment, and what factors are associated with poor postoperative functional outcomes scores and avascular necrosis (AVN) of the humeral head after ORIF? METHODS: Between June 2005 and December 2012, we surgically treated 774 patients for displaced two-, three-, and four-part PHFs. Approximately 75% (581 of 774) underwent ORIF, 10% (77 of 774) underwent hemiarthroplasty, 7% (54 of 774) underwent intramedullary nailing, 5% (39 of 774) underwent reverse shoulder arthroplasty, and the remaining 3% (23 of 774) underwent other surgical treatments. We considered those who had ORIF as potentially eligible. Based on that criterion, 75% (581) were eligible. However, only patients with nonosteoporotic three- and four-part PHFs (cortical thickness of the proximal humeral diaphysis greater than 6 mm on a preoperative AP radiograph of the affected shoulder) and a minimum of 10 years of follow-up were included. Sixty-four percent (498 of 774) of the patients were excluded because of simple or osteoporotic fractures, 1% (7 of 774) were excluded because of ipsilateral limb multiple fractures, 0.3% (2 of 774) were excluded because of pathologic PHFs, and another 2% (13 of 774) were lost before the minimum study follow-up of 10 years, leaving 8% (61 of 774) for analysis here. The mean age at surgery was 45 ± 12 years, with a mean follow-up of 13 years. Fifty-seven percent (35 of 61) of the patients were men. Patient-reported outcomes were evaluated using the University of California Loas Angeles (UCLA) score (range 0 to 35; higher scores represent better shoulder function) and Constant score (range 0 to 100; higher scores represent better shoulder function) at least 10 years postoperatively. Postoperative radiographs were reviewed to assess the cortical bone thickness of the proximal humerus, neck-shaft angle, head-to-tuberosity distance, and radiologically confirmable complications. Logistic regression analysis was performed to evaluate factors associated with poor postoperative functional scores (UCLA score ≤ 27 or Constant score ≤ 70) and AVN of the humeral head; the association between AVN and postoperative functional outcomes was also assessed. RESULTS: At the most-recent follow-up, these patients had a mean UCLA score of 31 ± 3 and a Constant score of 88 ± 10. The mean neck-shaft angle was 133° ± 10°, and 23% (14 of 61) of patients experienced AVN of the humeral head during follow-up. Twenty-nine complications in 30% (18 of 61) of patients were reported. After controlling for potentially confounding variables such as age and gender, we found that the presence of greater tuberosity malposition (odds ratio 18 [95% confidence interval 2 to 167]; p = 0.01) and immediate postoperative neck-shaft angle less than 130° (OR 19 [95% CI 3 to 127]; p = 0.002) were associated with poor postoperative functional scores. Four-part PHFs (OR 13 [95% CI 2 to 82]; p = 0.008) and metaphyseal extension less than 8 mm (OR 7 [95% CI 1 to 35]; p = 0.03) were associated with AVN of the humeral head. For patients who met the criteria for anatomic reduction (achievement of all of the following three criteria: neck-shaft angle ≥ 130°, head-shaft displacement < 5 mm, and head-to-tuberosity distance greater than or equal to 3 mm and less than or equal to 20 mm), there were no differences in postoperative functional scores between patients with AVN and those without. CONCLUSION: ORIF of nonosteoporotic proximal humeral fractures with locking plates led to favorable functional and radiologic outcomes at a minimum of 10 years of follow-up. When encountering complex PHFs in patients with good bone quality, every effort must be made to achieve an anatomic reduction of the fracture as far as possible, which may not reduce the risk of AVN (this occurred in nearly one-fourth of patients). However, good outcomes can usually be expected, even in patients with AVN. Because this was a retrospective study with a high risk of bias owing to sparse data, the factors associated with poor postoperative functional outcomes must be further investigated in large prospective studies. LEVEL OF EVIDENCE: Level III, therapeutic study.

Efficacy of Umbilical Cord-Derived Mesenchymal Stem Cells in the Treatment of Type 2 Diabetes Assessed by Retrospective Continuous Glucose Monitoring.

Umbilical cord-derived mesenchymal stem cells (UC-MSCs) have been proved a promising clinical strategy for the treatment of diabetes, and time in range (TIR) has been demonstrated a new metric of glycemic control links to diabetes complications. To further assess the therapeutic effect of UC-MSCs on TIR, a phase II study investigating the efficacy of UC-MSCs in Chinese adults with type 2 diabetes (T2D) assessed by retrospective continuous glucose monitoring (CGM) was conducted. In this randomized and placebo-controlled trial, a total of 73 patients were randomly assigned to receive intravenous infusion of UC-MSCs (n = 37) or placebo (n = 36) 3 times at 4-week intervals and followed up for 48 weeks. The primary endpoint was the changes in TIR and glycosylated hemoglobin (HbA1c). TIR and HbA1c were both significantly improved in UC-MSCs and placebo groups after 48 weeks of therapy compared with baseline. Compared with placebo group, UC-MSCs group exhibited more pronounced changes at 9 and 48 weeks from baseline in TIR (26.54 vs. 15.84 and 21.36 vs. 6.32) and HbA1c (-1.79 vs. -0.96 and -1.36 vs. -0.51). More patients in UC-MSCs group achieved the glycemic control target of TIR ≥ 70% and HbA1c < 7% at 9 and 48 weeks than in placebo group (59.5% vs. 27.8% and 43.2% vs. 11.1%). The C-peptide area under the curve (AUCC-pep) was an independent risk factor associated with efficacy in T2D undergoing UC-MSCs intervention. These results illustrate that UC-MSCs administration via intravenous infusion is an effective approach for ameliorating TIR.

Effect of HER2-low-positive status on neoadjuvant chemotherapy and survival outcome of breast cancer: a 10-year dual-center retrospective study.

Various novel HER2-targeted antibody-conjugated drugs (ADCs) have shown satisfactory antitumor activity in HER2-low-positive breast cancer (BC). It is urgent to clarify whether HER2-low-positive tumors have unique biological behavior and should be considered a new molecular subtype. We screened eligible BC patients and collected relevant information at the First Hospital of Jilin University and the First Affiliated Hospital of Xi'an Jiaotong University from January 2010 to December 2020. A total of 1027 patients were included in our study cohort, and 66.0% (678/1027) had HER2-low-positive tumors. Compared to HER2-zero patients, HER2-low-positive patients tended to have more lymph node metastasis, a larger proportion of hormone receptor (HR)-positive tumors, and a lower proliferation rate (Ki-67). The pathologic complete response (pCR) rate of HER2-low-positive patients was lower than that of HER2-zero patients (19.3% vs 26.1%), especially in the HR-positive subgroup (12.00% vs 20.29%). However, multivariate logistic regression analysis showed that HER2 status was not an independent factor for predicting pCR. HER2-low-positive patients had a higher overall survival (OS) rate in the HR-positive subgroup. The Cox regression model analysis suggested that HER2-low-positive status did not statistically significantly affect the survival outcomes, regardless of disease-free survival (DFS) (P=0.308) or OS (P=0.066). In conclusion, HER2-low-positive tumors have unique clinical and pathological characteristics, with a lower pCR rate in the HR-positive subgroup and better survival in the HR-negative subgroup compared to HER2-zero tumors. However, the effect of HER2-low-positive status on pCR or survival outcomes was not statistically significant.

A biocompatible NIR-II light-responsive nanoknife for permanent male sterilization.

Nanomaterial-mediated photothermal therapy (PTT) is a promising strategy for permanent male sterilization owing to its easy operation, rapid heating, minimal invasiveness, and high spatiotemporal controllability. However, the currently available PTT for male sterilization utilizes irradiation sources in the first near-infrared window (NIR-I), which may suffer from incomplete sterilization due to the insufficient penetration depth of NIR-I light. Herein, we developed a facile one-pot hydrothermal synthetic method of cysteine-coated copper sulfide (Cys-CuS) nanosheets for the second NIR window (NIR-II) PTT-mediated permanent male sterilization. In this method, Cys acted not only as a template but also as a sulfur resource in the formation of Cys-CuS nanosheets. The obtained Cys-CuS nanosheets possessed good photothermal properties and satisfied deep-tissue light response capacity under 1064 nm laser exposure. Given this, the permanent male sterilization in vivo was readily achieved by Cys-CuS nanosheets in a rapid manner (only 40 s). To the best of our knowledge, it is the first time that nanomaterial-mediated NIR-II PTT is applied for permanent male sterilization. We believe that the facilely prepared biocompatible Cys-CuS nanosheets can serve as a promising NIR-II light-responsive nanoknife to control the overpopulation of domestic pets and stray animals.

Surface Roughening of Irradiation-Activated Basalt Fiber through In Situ Growth of SiO2: Effects on Crystallization and Properties of PP Composites.

Basalt fiber (BF) is deemed a new environmentally friendly and high-performance fiber material due to its high strength, electrical insulation, corrosion resistance and high temperature resistance. Yet, the surface inertness restricts its practical application. In this work, the BF was irradiated and activated by electron beam, followed by in situ growth of SiO2 using a hydrothermal method, then composites with polypropylene (PP) were prepared by microinjection molding. According to the results of scanning electron microscopy (SEM) and Fourier transform infrared (FTIR), more active sites can be formed after irradiation, thus more SiO2 nanoparticles were generated on the surface of BF. Consequently, the rough surface of modified BF could provide stronger shear force during melt processing and resulted in a higher orientation of the molecular chains, increasing the lamellar thickness and generating more highly ordered ß crystals in the composites. I400BF-gSiO2 exhibited the highest content of ß crystals with the crystallinity of 53.62% and orientation of ß (300) crystal plane of 0.91, which were 8.66% and 0.04 higher than those of the composite with pristine BF. Furthermore, due to the perfection of crystals, increased interfaces and interfacial interlocking between PP molecules and modified BF, I400BF-gSiO2 showed good overall performance, with storage modulus of 8000 MPa at -100 °C, glass transition temperature of 23.03 °C and tensile strength of 62.2 MPa, which was 1900 MPa, 1.23 °C and 29.6 MPa higher than neat PP. Hence, the surface roughing strategy proposed in this work is expected to provide some insight and promote the application of BF reinforced thermoplastic composites.

Analysis of characteristics of four patients with adrenal unicentric Castleman disease.

Background: Castleman Disease (CD) is a group of diseases with characteristic lymph node histopathology, characterized by marked enlargement of deep or superficial lymph nodes. Adrenal CD is rarely reported, and an accurate preoperative diagnosis of adrenal CD is difficult. Method: We report four cases of CD in the adrenal gland confirmed by pathology and review the characteristics of this rare disease, highlighting the necessity of diagnostic evaluation and follow-up of the patients. Results: All of the patients sought medical advice because of adrenal incidentalomas. No significant abnormalities were presented in the biochemistry or endocrine systems. The imaging suggested a moderate-to-large mass with uneven moderate contrast enhancement of the adrenal region, similar to a pheochromocytoma. All cases were misdiagnosed as pheochromocytomas before operation and finally confirmed by histopathology. Three cases were pathologically diagnosed as hyaline vascular CD, and one case was diagnosed as plasma cell CD. All the patients are alive without recurrence after a median follow-up of 8 years. Conclusion: The adrenal CD should be considered after excluding pheochromocytoma and malignancy in the adrenal region. The long-term prognosis of patients with complete resection of the mass is excellent.

Clinical Application of a Resembling Rectangular Flap on Lateral Lip in Unilateral Cheiloplasty: A Modified Millard's Technique.

PURPOSE: This clinical study aimed to design and utilize a modified rotation-advancement technique (MRAT) with a resembling rectangular flap on the lateral lip for primary unilateral cheiloplasty and evaluated its postoperative outcomes. MATERIALS AND METHODS: A retrospective study was conducted on patients with a unilateral cleft lip who had undergone initial cheiloplasty with MRAT. The postoperative outcomes were assessed for nasolabial symmetry by photogrammetry. Repeated measures of ANOVA and two independent samples t tests were applied for statistical analysis. RESULTS: Twenty patients with unilateral cleft lip met the inclusion criteria. Postoperatively, the patients had well-shaped nasal sill and centered nasal columella. In addition to, the bilateral symmetrical ratios noticeably improved ( P <0.001). Simultaneously, the postoperative outcomes were independent of the cleft type and height differences of the two peaks ( P >0.05). CONCLUSIONS: Unilateral cheiloplasty using the present MRAT can better preserve the nasolabial structure and symmetry. The postoperative scar is concealed and simulates a normal philtral ridge.

The nodal positivity rate in breast pCR patients with initially, clinically node-negative breast cancer after neoadjuvant systemic therapy: A systematic review and meta-analysis.

Background: The 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. Objective: To 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. Methods: A 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. Results: The 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%). Conclusion: Our 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 Registration: https://www.crd.york.ac.uk/PROSPERO/#recordDetails, identifier CRD42022351739.

Evaluation of outcome of chemotherapy for breast cancer patients older than 70 years: A SEER-based study.

Background: With the aging of the population, the number of elderly breast cancer cases has increased. However, there is a lack of effective randomized clinical trial data to support whether elderly patients should receive chemotherapy. Our goal was to observe the relationship between chemotherapy and breast cancer-specific survival (BCSS) in elderly breast cancer patients and to identify those who could benefit from chemotherapy. Methods: We collected the data of patients who were diagnosed with invasive ductal carcinoma and older than 70 years in the SEER database from 1995 to 2016. The independent predictors of BCSS were identified by Cox regression analysis. Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were performed to eliminate confounding factors. Results: A total of 142,537 patients were collected, including 21,782 patients in the chemotherapy group and 120,755 patients in the non-chemotherapy group. We identified the same potential predictors of BCSS after PSM and IPTW, such as age, race, grade, stage, therapy, subtype. A nomogram for predicting 3-year, 5-year and 10-year BCSS was constructed. The 3-year, 5-year and 10-year AUCs of the nomogram were 0.842, 0.819, and 0.788. According to the risk stratification of model predictive scores, patients in the high-risk group achieved the greatest improvement in BCSS after receiving chemotherapy. Conclusions: Our study suggests that women older than 70 years with larger tumors, higher grade, positive nodes, negative hormone receptor and inactive local therapy gain prognostic benefits from chemotherapy, but for those with low- and median-risk, conventional chemotherapy should be administered cautiously.

The outcome of neoadjuvant chemotherapy and the current trend of surgical treatment in young women with breast cancer: A multicenter real-world study (CSBrS-012).

Background and objectives: The 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. Methods: The 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. Results: A 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. Conclusion: Breast 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.

Enzyme-trigger ratiometric fluorescent nanoplatform for diagnosis and imaging of oral diseases.

Oral health is an essential part of overall health. Matrix metalloproteinase-2 (MMP-2) is a potential biomarker for diseases. The ability to accurately detect MMP-2 in vivo and in vitro is of great importance for the early diagnosis and prognosis, as well as the treatment evaluation, of oral diseases. In this study, cyanine 3 (Cy3) polypeptide containing the specific peptide substrate (PLGVR) of MMP-2 was modified onto SiO2-coated upconversion nanoparticles to fabricate a fluorescence resonance energy transfer (FRET)-based ratiometric fluorescent nanoplatform (UCNPs@SiO2@Cy3-pep). The green upconversion luminescence of UCNPs@SiO2 is quenched by Cy3, while its red upconversion luminescence is undisturbed. After Cy3 is cleaved at the PLGVR peptide by MMP-2, it is detached from the surface of UCNPs@SiO2, resulting in the recovery of green luminescence. Based on this principle, we applied UCNPs@SiO2@Cy3-pep to detect MMP-2 activity in different oral disease samples and models. We found that the level of MMP-2 in saliva of patients with oral cancer was 10 times higher than that of healthy individuals. In addition, the MMP-2 level in patients with periodontitis and severe dental caries also increased to varying degrees compared with that in healthy patients. Finally, in vitro and in vivo imaging experiments revealed that the nanoplatform was effective in monitoring MMP-2 level. Together, the developed nanoplatform can be an ideal tool for medical diagnosis of MMP-2-related diseases.

Elevated ADAM-like Decysin-1 (ADAMDEC1) expression is associated with increased chemo-sensitivity and improved prognosis in breast cancer patients.

Background: Chemoresistance is problematic and its mechanisms are unclear in breast cancer. More predictive markers are urgently required. Methods: GSE32646, GSE34138, and GSE20271 were downloaded from the Gene Expression Omnibus (GEO) database to identify differentially expressed genes (DEGs) between chemosensitive and chemoresistant tumors. LinkedOmics was used to analyze ADAM-like Decysin-1 (ADAMDEC1) expression among patients with different clinical characteristics and detect co-expression genes for functional analysis. Tumor Immune Estimation Resource (TIMER) and an integrated repository portal for tumor-immune system interactions (TISIDB) were used to investigate the association between the target gene and the immune response. Gene Set Cancer Analysis (GSCA) was utilized to explore the related pathways of ADAMDEC1 and evaluate the correlation between the expression of ADAMDEC1 and drug sensitivity. RNA22, miRWalk, and miRmap were used to predict the upstream micro ribonucleic acids (miRNAs) regulating ADAMDEC1 expression, while DIANA-LncBase v2 was applied to predict the upstream long non-coding ribonucleic acids (lncRNAs). Kaplan-Meier curve analysis was applied to determine the survival time. Results: We identified that ADAMDEC1 was upregulated among chemosensitive triple-negative breast cancer (TNBC) tissues in GSE32646, GSE34138, and GSE20271. Higher expression of ADAMDEC1 indicated longer survival in breast cancer. Next, we found that ADAMDEC1 was significantly related to the immune response in breast cancer through functional enrichment analysis and further meta-data validation. Moreover, we recognized that hsa-miR-4534 was the potential upstream miRNA regulating ADAMDEC1 expression and Taurine Up-Regulated 1 (TUG1) was the most likely upstream lncRNA of ADAMDEC1 and hsa-miR-4534. Finally, the correlation between ADAMDEC1 and chemosensitivity was confirmed through drug database analysis. Conclusions: Elevated ADAMDEC1 expression is associated with increased chemosensitivity and better prognosis in breast cancer patients.

ASGARD is A Single-cell Guided Pipeline to Aid Repurposing of Drugs.

Single-cell RNA sequencing technology has enabled in-depth analysis of intercellular heterogeneity in various diseases. However, its full potential for precision medicine has yet to be reached. Towards this, we propose A Single-cell Guided Pipeline to Aid Repurposing of Drugs (ASGARD) that defines a drug score to recommend drugs by considering all cell clusters to address the intercellular heterogeneity within each patient. ASGARD shows significantly better average accuracy on single-drug therapy compared to two bulk-cell-based drug repurposing methods. We also demonstrated that it performs considerably better than other cell cluster-level predicting methods. In addition, we validate ASGARD using the drug response prediction method TRANSACT with Triple-Negative-Breast-Cancer patient samples. We find that many top-ranked drugs are either approved by the Food and Drug Administration or in clinical trials treating corresponding diseases. In conclusion, ASGARD is a promising drug repurposing recommendation tool guided by single-cell RNA-seq for personalized medicine. ASGARD is free for educational use at https://github.com/lanagarmire/ASGARD .

An easily achievable strategy to promote the penetration of methylene blue into dentinal tubules.

BACKGROUND: One critical issue that impairs the therapeutic effects of antimicrobial photodynamic therapy (aPDT) in root canal disinfection is the insufficient penetration of photosensitizer into dentinal tubules. Therefore, this study aimed to compare the treatments in enhancing photosensitizers' penetrability for aPDT in root canal therapy. METHODS: Thirty premolars with a single root canal were randomly divided into three groups (n = 10), using Methylene blue (MB) as a photosensitizer and treated with different approaches: sonic-assisted diffusing group, ultrasonic-assisted diffusing group and the control without treatment. All specimens were observed by stereomicroscope to measure the penetration depth of MB into dentinal tubules. RESULTS: Both sonic and ultrasonic treatments substantially improved the penetrability of MB. The former achieved a deeper penetration depth than the latter did in the same region of root (P<0.05). Regarding the dye penetration depths at different root regions, the control group showed a declining trend from coronal to apical. In contrast, the penetration depths of sonic and ultrasonic-assisted diffusing groups from highest to lowest were middle > coronal > apical (P<0.05). CONCLUSIONS: This study showed that both sonic and ultrasonic treatments remarkably promoted MB's penetration depth into dentinal tubules. Maximum penetration was achieved when treated with a sonic approach.