Proteomics appending a complementary dimension to precision oncotherapy.

Recent advances in high-throughput proteomic profiling technologies have facilitated the precise quantification of numerous proteins across multiple specimens concurrently. Researchers have the opportunity to comprehensively analyze the molecular signatures in plentiful medical specimens or disease pattern cell lines. Along with advances in data analysis and integration, proteomics data could be efficiently consolidated and employed to recognize precise elementary molecular mechanisms and decode individual biomarkers, guiding the precision treatment of tumors. Herein, we review a broad array of proteomics technologies and the progress and methods for the integration of proteomics data and further discuss how to better merge proteomics in precision medicine and clinical settings.

Does the Dose of Standard Adjuvant Chemotherapy Affect the Triple-negative Breast Cancer Benefit from Extended Capecitabine Metronomic Therapy? An Exploratory Analysis of the SYSUCC-001 Trial.

Purpose: Results from studies of extended capecitabine after the standard adjuvant chemotherapy in early stage triple-negative breast cancer (TNBC) were inconsistent, and only low-dose capecitabine from the SYSUCC-001 trial improved disease-free survival (DFS). Adjustment of the conventional adjuvant chemotherapy doses affect the prognosis and may affect the efficacy of subsequent treatments. This study investigated whether the survival benefit of the SYSUCC-001 trial was affected by dose adjustment of the standard adjuvant chemotherapy or not. Patients and Methods: We reviewed the adjuvant chemotherapy regimens before the extended capecitabine in the SYSUCC-001 trial. Patients were classified into "consistent" (standard acceptable dose) and "inconsistent" (doses lower than acceptable dose) dose based on the minimum acceptable dose range in the landmark clinical trials. Cox proportional hazards model was used to investigate the impact of dose on the survival outcomes. Results: All 434 patients in SYSUCC-001 trial were enrolled in this study. Most of patients administered the anthracycline-taxane regimen accounted for 88.94%. Among patients in the "inconsistent" dose, 60.8% and 47% received lower doses of anthracycline and taxane separately. In the observation group, the "inconsistent" dose of anthracycline and taxane did not affect DFS compared with the "consistent" dose. Moreover, in the capecitabine group, the "inconsistent" anthracycline dose did not affect DFS compared with the "consistent" dose. However, patients with "consistent" taxane doses benefited significantly from extended capecitabine (P=0.014). The sufficient dose of adjuvant taxane had a positive effect of extended capecitabine (hazard ratio [HR] 2.04; 95% confidence interval [CI] 1.02 to 4.06). Conclusion: This study found the dose reduction of adjuvant taxane might negatively impact the efficacy of capecitabine. Therefore, the reduction of anthracycline dose over paclitaxel should be given priority during conventional adjuvant chemotherapy, if patients need dose reduction and plan for extended capecitabine.

Cocirculation and coinfection of multiple respiratory viruses during autumn and winter seasons of 2023 in Beijing, China: A retrospective study.

China experienced severe epidemics of multiple respiratory pathogens in 2023 after lifting "Zero-COVID" policy. The present study aims to investigate the changing circulation and infection patterns of respiratory pathogens in 2023. The 160 436 laboratory results of influenza virus and respiratory syncytial virus (RSV) from February 2020 to December 2023, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from June 2020 to December 2023, Mycoplasma pneumoniae, adenovirus, and human rhinovirus from January 2023 to December 2023 were analyzed. We observed the alternating epidemics of SARS-CoV-2 and influenza A virus (IAV), as well as the out-of-season epidemic of RSV during the spring and summer of 2023. Cocirculation of multiple respiratory pathogens was observed during the autumn and winter of 2023. The susceptible age range of RSV in this winter epidemic (10.5, interquartile range [IQR]: 5-30) was significantly higher than previously (4, IQR: 3-34). The coinfection rate of IAV and RSV in this winter epidemic (0.695%) was significantly higher than that of the last cocirculation period (0.027%) (p < 0.001). Similar trend was also found in the coinfection of IAV and SARS-CoV-2. The present study observed the cocirculation of multiple respiratory pathogens, changing age range of susceptible population, and increasing coinfection rates during the autumn and winter of 2023, in Beijing, China.

Spurious High Platelet Count without PLT Flag(S) in a Patient with Severe Aplastic Anaemia.

BACKGROUND: Platelet (PLT) count is one of the most important parameters of automated hematology, as spurious PLT reports could affect medical judgement and bring significant risks. In most cases, spurious PLT will not be reported for review criteria, which will be triggered by abnormal PLT histograms and PLT flag(s). Here, we present a case of severe aplastic anemia after hematopoietic stem cell transplantation with spurious high platelet count with normal histogram and no PLT flag(s). METHODS: The electrical impedance channel (PLT-I) and the fluorescence channel (PLT-F) of Sysmex XN-series hematology analyzer was used to obtain PLT results. Then, the sample was retested by another hematology analyzer MINDRAY BC-7500 [NR] CRP, and incubation was performed to rule out cryoglobulin interference. Furthermore, a microscope was used to estimate the PLT count by the ratio of platelets to red blood cells and observe the morphology of cells. RESULTS: Both PLT-I and PLT-F test results were spuriously high, and microscopically assessed platelet counts were relatively reliable. The observed spiny cells and ghost cells caused by hemolysis may have contributed to the inaccuracy of instrumental counting in this case. CONCLUSIONS: For special hematologic patients, PLT-I with flags may not be sufficient for screening purposes and PLT-F is not always accurate. Multiple testing methods including manual microscopy are needed.

Advancing predictive markers in lung adenocarcinoma: A machine learning-based immunotherapy prognostic prediction signature.

The prognosis of lung adenocarcinoma (LUAD) is generally poor. Immunotherapy has emerged as a promising therapeutic modality, demonstrating remarkable potential for substantially prolonging the overall survival of individuals afflicted with LUAD. However, there is currently a lack of reliable signatures for identifying patients who would benefit from immunotherapy. We conducted a comparative analysis of two immunotherapy cohorts (OAK and POPLAR) and utilized single-factor COX regression to identify genes that significantly impact the prognosis of LUAD. Based on the TCGA-LUAD dataset, we employed a combination of 101 machine learning algorithms to construct a model and selected the optimal model. The model was validated on five GEO datasets and compared with 144 previously published signatures to assess its performance. Subsequently, we explored the underlying biological mechanisms through tumor mutation burden analysis, enrichment analysis, and immune infiltration analysis. An immunotherapy prognostic prediction signature (IPPS) was constructed based on 13 genes, showing robust performance in the TCGA-LUAD dataset. IPPS exhibited consistent predictive accuracy in the validation cohorts. Compared to 144 previously published signatures, IPPS consistently ranked among the top in terms of C-index values. Further exploration revealed differences between high and low-IPPS groups in terms of tumor mutation burden, pathway enrichment, and immune infiltration. IPPS demonstrates strong predictive capabilities for the prognosis of LUAD patients, offering the potential to identify suitable candidates for immunotherapy and contribute to precision treatment strategies for LUAD.

Spatiotemporal transformable nano-assembly for on-demand drug delivery to enhance anti-tumor immunotherapy.

Induction of tumor cell senescence has become a promising strategy for anti-tumor immunotherapy, but fibrotic matrix severely blocks senescence inducers penetration and immune cells infiltration. Herein, we designed a cancer-associated fibroblasts (CAFs) triggered structure-transformable nano-assembly (HSD-P@V), which can directionally deliver valsartan (Val, CAFs regulator) and doxorubicin (DOX, senescence inducer) to the specific targets. In detail, DOX is conjugated with hyaluronic acid (HA) via diselenide bonds (Se-Se) to form HSD micelles, while CAFs-sensitive peptide is grafted onto the HSD to form a hydrophilic polymer, which is coated on Val nanocrystals (VNs) surface for improving the stability and achieving responsive release. Once arriving at tumor microenvironment and touching CAFs, HSD-P@V disintegrates into VNs and HSD micelles due to sensitive peptide detachment. VNs can degrade the extracellular matrix, leading to the enhanced penetration of HSD. HSD targets tumor cells, releases DOX to induce senescence, and recruits effector immune cells. Furthermore, senescent cells are cleared by the recruited immune cells to finish the integrated anti-tumor therapy. In vitro and in vivo results show that the nano-assembly remarkably inhibits tumor growth as well as lung metastasis, and extends tumor-bearing mice survival. This work provides a promising paradigm of programmed delivering multi-site nanomedicine for cancer immunotherapy.

Preliminary Efficacy of a Cognitive Behavioral Therapy-Based Smartphone App for Smoking Cessation in China: Randomized Controlled Pilot Trial.

BACKGROUND: The overall prevalence of cigarette smokers in China is very high, and China's total cigarette consumption makes up more than 40% of the world's consumption. In view of the lack of smoking cessation services and social support in China and the effectiveness of mobile phone apps for quitting smoking in other countries, we carried out a smartphone app-based smoking cessation trial in China. OBJECTIVE: This study aimed to evaluate the efficacy of a cognitive behavioral therapy (CBT)-based smoking cessation smartphone app among smokers seeking treatment in China. METHODS: We conducted a randomized controlled, web-based pilot clinical trial in China between February 23 and June 27, 2021. Eligible participants were randomly assigned to the smoking cessation app intervention group or the control group in a ratio of 1:1. The intervention group received the CBT smoking cessation intervention using a smartphone app, and the control group received a "thank you" message. The intervention was 4 weeks long, and the patients were followed up for 4 weeks. The primary outcome was self-reported continuous smoking abstinence at week 4 after the quit date. The secondary outcomes included self-reported 7-day point prevalence of smoking abstinence; reduction of the number of cigarettes smoked per day at weeks 1, 2, 3, and 4; and program acceptability. RESULTS: A total of 973 people were recruited to quit smoking, of whom 262 completed basic information, 56 were excluded, and 206 were randomized and included in the final analysis. There were 189 (91.7%) men and 17 (8.3%) women, with an average age of 34.46 (SD 7.53) years and an average daily smoking rate of 15.93 (SD 7.10) cigarettes/day. We found 30 (29.7%) of the 101 participants in the intervention group and 7 (6.7%) of the 105 participants in the control group reported continuous smoking cessation after the quit date at week 4 (odds ratio 5.92, 95% CI 3.78-9.26; P<.001). The 7-day point prevalence abstinence rate of the intervention group varied from 42.6% (43/101) to 46.5% (47/101) after 1, 2, 3, and 4 weeks, while the control group varied from 18.1% (19/105) to 26.7% (28/105). Compared to the control group, continued smokers consumed 1.5-3.0 fewer cigarettes per day in the intervention group. The overall program got positive user feedback with a high satisfaction rate (66/87, 76%) and an average Mobile Application Rating Scale user version score of 3.46. CONCLUSIONS: Our pilot study provided preliminary evidence that the CBT-based smoking cessation smartphone app led to improved smoking quit rates versus control in Chinese smokers. The study demonstrated the CBT-based smartphone app may be an effective and feasible digital treatment model to help smokers quit, which may improve smoking cessation service quality and accessibility in China. TRIAL REGISTRATION: ClinicalTrials.gov NCT04421170; https://clinicaltrials.gov/study/NCT04421170. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1136/bmjopen-2020-041985.

Ultrafine grinding improves the nutritional, physicochemical, and antioxidant activities of two varieties of whole-grain highland barley.

Effects of ultrafine grinding on the nutritional profile, physicochemical properties, and antioxidant activities of whole-grain highland barley (HB) including white highland barley (WHB) and black highland barley (BHB) were studied. Whole-grain HB was regularly ground and sieved through 80 mesh get 80 M powder, and HB was ultrafine grounded and sieved through 80 mesh, 150 mesh, and 200 mesh get 80UMM, 150UMM, and 200UMM samples. Particle size of WHB and BHB reduced significantly after ultrafine grinding. As the particle size decreased, moisture content of WHB and BHB decreased significantly, whereas fat content increased significantly. Redistribution of fiber components in WHB and BHB from insoluble to soluble fractions was also observed. Wherein, content of soluble pentosan of WHB and BHB increased significantly from 0.56% and 0.78% (80 M) to 0.91% and 1.14% (200UMM), respectively. Damaged starch of WHB and BHB increased significantly from 8.16% and 8.21% (80 M) to 10.29% and 10.07% (200UMM), respectively. Content of phenolic acid and flavonoid of WHB and BHB and associated antioxidant capacity were increased after ultrafine grinding. Color of L* value increased significantly, a* and b* values decreased significantly, indicating the whiteness of WHB and BHB was increased after ultrafine grinding. Pasting temperature of WHB and BHB decreased, whereas peak viscosity increased. X-ray diffraction patterns of HB showed typical A- and V-style polymorphs and the relative crystallinity of HB decreased as the particle size decreased. Taken together, ultrafine grinding has shown great potential in improving the nutritional, physiochemical, and antioxidant properties of whole-grain HB. Our research findings could help better understand the ultrafine grinded whole grain HB in food industry.

Current treatment strategies targeting histone deacetylase inhibitors in acute lymphocytic leukemia: a systematic review.

Acute lymphocytic leukemia is a hematological malignancy that primarily affects children. Long-term chemotherapy is effective, but always causes different toxic side effects. With the application of a chemotherapy-free treatment strategy, we intend to demonstrate the most recent results of using one type of epigenetic drug, histone deacetylase inhibitors, in ALL and to provide preclinical evidence for further clinical trials. In this review, we found that panobinostat (LBH589) showed positive outcomes as a monotherapy, whereas vorinostat (SAHA) was a better choice for combinatorial use. Preclinical research has identified chidamide as a potential agent for investigation in more clinical trials in the future. In conclusion, histone deacetylase inhibitors play a significant role in the chemotherapy-free landscape in cancer treatment, particularly in acute lymphocytic leukemia.

miR-539-5p targets BMP2 to regulate Treg activation in B-cell acute lymphoblastic leukemia through TGF-ß/Smads/MAPK.

MicroRNAs (mRNAs) were believed to play an important role in cancers, and this study aimed to explore the mechanism of miRNA regulating Treg in B-cell acute lymphoblastic leukemia (B-ALL). Firstly, the differentially expressed miRNAs and target genes significantly associated with Tregs were screened out by high-throughput sequencing, and their enrichment pathways were analyzed. The binding relationship between miRNA and target genes was further verified, and the effects of miRNA on the proliferation and apoptosis of B-ALL Nalm-6 cells and Treg activation were analyzed. Results showed that differentially expressed miR-539-5p was significantly under-expressed, and its target gene BMP2 was significantly over-expressed in B-ALL, and significantly enriched in the TGF-ß1 pathway. In addition, both miR-539-5p and BMP2 were significantly correlated with Treg activity in B-ALL. In vitro experiments further confirmed that miR-539-5p could directly target BMP2. The low expression of miR-539-5p in B-ALL significantly promoted BMP2 expression to promote the proliferation and inhibit apoptosis of Nalm-6 cells. Furthermore, the high expression of BMP2 in B-ALL could cooperate with TGF-ß1 to promote the activation of human CD4+CD25-T cells to Treg, and significantly activate the TGF-ß/Smads/MAPK pathway. In vivo experiments also confirmed that overexpression of miR-539-5p significantly inhibited BMP2 to suppress Treg activation and Smad1 and Smad2 phosphorylation, and finally inhibit the B-ALL process. In conclusion, miR-539-5p was significantly under-expressed in B-ALL and could target BMP2 to promote its expression, and the overexpressed BMP2 further promoted Treg activation in B-ALL by regulating TGF-ß/Smads/MAPK pathway.

Arthroscopic debridement and reduction is an effective procedure for failed closed reduction in young children with developmental dislocation of the hip.

PURPOSE: To assess the efficacy of arthroscopic debridement and reduction through two medial portals for the treatment of developmental dislocation of the hip (DDH) with failure of initial closed reduction and to explore key pathological structures obstructing reduction. METHODS: Forty-eight children with 58 irreducible dislocated hips treated by arthroscopic reduction between January 2017 and December 2020 were retrospectively evaluated. Arthroscopic reduction was performed via two medial portals located in the superior and inferior adductor longus. All intra-articular obstacles were eliminated via arthroscopy, followed by manual reduction and spica cast immobilization. The surgical duration, extent of improvement in the safe zone, and extent of secondary surgical treatment were noted. All the children were followed up for > 24 months. Hip function and radiographic outcomes were evaluated. RESULTS: All 58 hips showed safe zone improvement and concentric reduction after arthroscopic debridement. Hypertrophic ligamentum teres and thickened pulvinars were detected and resected in all hips. Constrictive capsules preventing reduction were observed in 15 hips, which needed to be further released. No inverted labrum was observed. Secondary surgery was performed in four hips with redislocation and seven hips with subluxation during follow-up. The remaining 47 hips (81.03%) maintained their reduction at the last follow-up. Excellent and good clinical outcomes were achieved in 95.74% of patients according to McKay's criteria. Two hips, three hips, and one hip were diagnosed with grade I, II, and III osteonecrosis of the femoral head, respectively. CONCLUSION: This study demonstrated that arthroscopic debridement and reduction is a safe and feasible choice for treating irreducible DDH.

A common allele increases endometrial Wnt4 expression, with antagonistic implications for pregnancy, reproductive cancers, and endometriosis.

The common human SNP rs3820282 is associated with multiple phenotypes including gestational length and likelihood of endometriosis and cancer, presenting a paradigmatic pleiotropic variant. Deleterious pleiotropic mutations cause the co-occurrence of disorders either within individuals, or across population. When adverse and advantageous effects are combined, pleiotropy can maintain high population frequencies of deleterious alleles. To reveal the causal molecular mechanisms of this pleiotropic SNP, we introduced this substitution into the mouse genome by CRISPR/Cas 9. Previous work showed that rs3820282 introduces a high-affinity estrogen receptor alpha-binding site at the Wnt4 locus. Here, we show that this mutation upregulates Wnt4 transcription in endometrial stroma, following the preovulatory estrogen peak. Effects on uterine transcription include downregulation of epithelial proliferation and induction of progesterone-regulated pro-implantation genes. We propose that these changes increase uterine permissiveness to embryo invasion, whereas they decrease resistance to invasion by cancer and endometriotic foci in other estrogen-responsive tissues.

RBMS1 Coordinates with the m6A Reader YTHDF1 to Promote NSCLC Metastasis through Stimulating S100P Translation.

Metastasis is the leading cause for the high mortality of lung cancer, however, effective anti-metastatic drugs are still limited. Here it is reported that the RNA-binding protein RBMS1 is positively associated with increased lymph node metastasis in non-small cell lung cancer (NSCLC). Depletion of RBMS1 suppresses cancer cell migration and invasion in vitro and inhibits cancer cell metastasis in vivo. Mechanistically, RBMS1 interacts with YTHDF1 to promote the translation of S100P, thereby accelerating NSCLC cell metastasis. The RRM2 motif of RBMS1 and the YTH domain of YTHDF1 are required for the binding of RBMS1 and YTHDF1. RBMS1 ablation inhibits the translation of S100P and suppresses tumor metastasis. Targeting RBMS1 with NTP, a small molecular chemical inhibitor of RBMS1, attenuates tumor metastasis in a mouse lung metastasis model. Correlation studies in lung cancer patients further validate the clinical relevance of the findings. Collectively, the study provides insight into the molecular mechanism by which RBMS1 promotes NSCLC metastasis and offers a therapeutic strategy for metastatic NSCLC.

Gradient Rotating Magnetic Fields Impairing F-Actin-Related Gene CCDC150 to Inhibit Triple-Negative Breast Cancer Metastasis by Inactivating TGF-ß1/SMAD3 Signaling Pathway.

Triple-negative breast cancer (TNBC) is the most aggressive and lethal malignancy in women, with a lack of effective targeted drugs and treatment techniques. Gradient rotating magnetic field (RMF) is a new technology used in oncology physiotherapy, showing promising clinical applications due to its satisfactory biosafety and the abundant mechanical force stimuli it provides. However, its antitumor effects and underlying molecular mechanisms are not yet clear. We designed two sets of gradient RMF devices for cell culture and animal handling. Gradient RMF exposure had a notable impact on the F-actin arrangement of MDA-MB-231, BT-549, and MDA-MB-468 cells, inhibiting cell migration and invasion. A potential cytoskeleton F-actin-associated gene, CCDC150, was found to be enriched in clinical TNBC tumors and cells. CCDC150 negatively correlated with the overall survival rate of TNBC patients. CCDC150 promoted TNBC migration and invasion via activation of the transforming growth factor ß1 (TGF-ß1)/SMAD3 signaling pathway in vitro and in vivo. CCDC150 was also identified as a magnetic field response gene, and it was marked down-regulated after gradient RMF exposure. CCDC150 silencing and gradient RMF exposure both suppressed TNBC tumor growth and liver metastasis. Therefore, gradient RMF exposure may be an effective TNBC treatment, and CCDC150 may emerge as a potential target for TNBC therapy.

A pancancer analysis of histone deacetylase 3 in human tumors.

Background: Histone deacetylase 3 (HDAC3) is known to be an important role in various kinds of cancer, but its effect has not been examined on the pancancer level. Thus, a systematic pancancer analysis was conducted to explore its potential role in pancancer diagnosis, prognosis, and immune correlation research. Methods: We used a series of databases including The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx) Project, The University of Alabama at Birmingham Cancer data analysis portal (UALCAN), Tumor Immune Estimation Resource (TIMER), and Search Tool for the Retrieval of Interacting Genes/Proteins (STRING), among others, to analyze the relationship between the expression of HDAC3 and the diagnosis and prognosis of cancer, the tumor microenvironment (TME), immune infiltration, tumor mutational burden (TMB), microsatellite instability (MSI), mismatch repair (MMR) system using various bioinformatics methods. Downstream pathways of HDAC3 were identified by gene set enrichment analysis (GSEA). Furthermore, the protein expression of HDAC3 in tumor tissues and normal tissues of 17 patients with gliomas was analyzed via western blotting. Results: The expression of HDAC3 changed in most types of tumors, which was closely related to most tumor diagnoses and negatively related to some patients' overall survival (OS) and recurrence-free survival (RFS). The pan-cancer analysis demonstrated that it was tightly correlated to DNA methylation and RNA methylation modifications and associated with TMB and MSI. The expression level of HDAC3 was positively correlated with many immune checkpoint molecules and regulators and positively associated with the infiltration levels of immune cells in the TME in most tumor types. Furthermore, enrichment analysis revealed that transcriptional misregulation in cancer and RNA splicing functions were involved in the functional mechanism of HDAC3-related genes. Experimental research showed that the protein expression of HDAC3 was elevated in tumor tissues of patients with glioma. Conclusions: Through our comprehensive bioinformatics analysis, we evaluated the role of HDAC3 in pancancer, and our findings suggest that it may be an indicator for some cancer diagnoses and influence immune balance.

Assessing Diagnostic Performance Using the Transverse Plane Plus Coronal Plane Compared With the Transverse Plane Alone in Screening Automated Breast Ultrasound.

OBJECTIVES: The coronal plane is the unique display mode of automated breast (AB) ultrasound (US), which has valuable features of showing the entire breast anatomy and providing additional diagnostic value for breast lesions. However, whether adding the coronal plane could improve the diagnostic performance in screening breast cancer remains uncertain. This study aimed to evaluate the value of adding the coronal plane in interpretation for AB US screening. METHODS: In this retrospective study, AB US images from 644 women (396 in the no-finding group, 143 with benign lesions, and 105 with malignant lesions) aged 40-70 years were collected between January 2016 and October 2020. Four novice radiologists (with 1-5 years of experience with breast US) and four experienced radiologists (with >5 years of experience with breast US) were assigned to read all AB US images in the transverse plane plus coronal plane (T + C planes) and transverse plane (T plane) alone in separate reading sessions. Diagnostic performance, lesion conspicuity, and reading time were compared using analysis of variance. RESULTS: The mean reading time of all radiologists was significantly shorter in the T + C planes reading mode than in the T plane alone (115 ± 32 vs 128 ± 31 s, respectively; P < .05), and cancers had a higher conspicuity (odds ratio, 1.76; 95% confidence interval [CI], 1.00-3.08; P = .04). No significant differences were noted in the two reading modes (T + C planes vs T plane) in the sensitivity (82% [95% CI, 74-89%] vs 81% [95% CI, 74-88%], respectively; P = .68) and specificity (68% [95% CI, 62-75%] vs 70% [95% CI, 64-75%], respectively; P = .39) when Breast Imaging-Reporting and Data System (BI-RADS) 3 was set as the threshold. There were also no significant differences in the two reading modes (T + C planes vs T plane) in the sensitivity (70% [95% CI, 64-76%] vs 69% [95% CI, 63-75%], respectively; P = .39) and specificity (91% [95% CI, 87-96%] vs 91% [95% CI, 88-95%], respectively; P = .90) when BI-RADS 4 was set as the threshold. In addition, the mean areas under the receiver operating characteristic curves of all radiologists in the two reading modes (T + C planes vs T plane) were not significantly different (0.84 [95% CI, 0.79-0.89] vs 0.83 [95% CI, 0.78-0.89], respectively; P = .61). CONCLUSIONS: Adding a coronal plane in the AB US screening setting saved the reading time and improved the conspicuity of breast cancers but not the diagnostic performance.

Effect of Huaier granule on prognosis of breast cancer: A single-center propensity score matching retrospective study.

BACKGROUND: Huaier granule is an important medicinal fungus extract widely used in cancer treatment. Previous retrospective studies have reported its effectiveness in breast cancer patients, but the imbalanced baseline characteristics of participants could have biased the results. Therefore, this retrospective study aimed to examine the efficacy of Huaier granule on the prognosis of breast cancer patients. METHODS: In this single-center cohort study, breast cancer patients diagnosed and treated at the Guangdong Provincial Hospital of Chinese Medicine between 2009 and 2017 were selected. The data were retrospectively analyzed and divided into two groups according to whether the patients received Huaier granules. The propensity score matching (PSM) method was used to eliminate selection bias. The disease-free survival (DFS) and overall survival (OS) for these groups were compared using the Kaplan-Meier method and the Cox regression. RESULTS: This study included 214 early invasive breast cancer patients, 107 in the Huaier group and 107 in the control group. In the Kaplan-Meier analysis, the 2-year and 5-year DFS rates were significantly different in the Huaier group and control group (hazard ratio [HR], 0.495; 95% confidence interval [CI], 0.257-0.953; P = 0.023). The 2-year and 5-year OS rates were also significantly different (HR, 0.308; 95% CI, 0.148-0.644; P = 0.001). On multivariable Cox regression, Huaier granule was associated with improved DFS (HR, 0.440; 95% CI, 0.223-0.868; P = 0.018) and OS (HR, 0.236; 95% CI, 0.103-0.540; P = 0.001). CONCLUSION: In this retrospective study, Huaier granules improved the DFS and OS of early invasive breast cancer patients, providing real-world evidence for further prospective studies on treating breast cancer with Huaier granules.

Uncovering impaired mitochondrial and lysosomal function in adipose-derived stem cells from obese individuals with altered biological activity.

BACKGROUND: Adipose-derived stem cells (ADSCs) have been extensively used in preclinical and clinical trials for treating various diseases. However, the differences between ADSCs from lean individuals (L-ADSCs) and those from obese individuals (O-ADSCs) have not been thoroughly investigated, particularly regarding their mitochondrial and lysosomal functions. Therefore, this study aims to evaluate the differences between L-ADSCs and O-ADSCs in terms of cell biological activity, mitochondria, and lysosomes. METHODS: We first isolated and cultured L-ADSCs and O-ADSCs. We then compared the differences between the two groups in terms of biological activity, including cell proliferation, differentiation potential, and their effect on the polarization of macrophages. Additionally, we observed the mitochondrial and lysosomal morphology of ADSCs using an electronic microscope, MitoTracker Red, and lysotracker Red dyes. We assessed mitochondrial function by examining mitochondrial membrane potential and membrane fluidity, antioxidative ability, and cell energy metabolism. Lysosomal function was evaluated by measuring autophagy and phagocytosis. Finally, we performed transcriptome analysis of the ADSCs using RNA sequencing. RESULTS: The biological activities of O-ADSCs were decreased, including cell immunophenotypic profiles, cell proliferation, and differentiation potential. Furthermore, compared to L-ADSCs, O-ADSCs promoted M1-type macrophage polarization and inhibited M2-type macrophage polarization. Additionally, the mitochondrial morphology of O-ADSCs was altered, with the size of the cells becoming smaller and mitochondrial fragments increasing. O-ADSCs also exhibited decreased mitochondrial membrane potential and membrane fluidity, antioxidative ability, and energy metabolism. With respect to lysosomes, O-ADSCs contained ungraded materials in their lysosomes, enhanced lysosomal permeability, and reduced autophagy and phagocytosis ability. RNA sequence analysis indicated that the signalling pathways related to cell senescence, cancer, and inflammation were upregulated, whereas the signalling pathways associated with stemness, cell differentiation, metabolism, and response to stress and stimuli were downregulated. CONCLUSIONS: This study indicates that ADSCs from individuals (BMI > 30 kg/m2) exhibit impaired mitochondrial and lysosomal function with decreased biological activity.