Individualized prediction of non-sentinel lymph node metastasis in Chinese breast cancer patients with ≥ 3 positive sentinel lymph nodes based on machine-learning algorithms.

BACKGROUND: Axillary lymph node dissection (ALND) is a standard procedure for early-stage breast cancer (BC) patients with three or more positive sentinel lymph nodes (SLNs). However, ALND can lead to significant postoperative complications without always providing additional clinical benefits. This study aims to develop machine-learning (ML) models to predict non-sentinel lymph node (non-SLN) metastasis in Chinese BC patients with three or more positive SLNs, potentially allowing the omission of ALND. METHODS: Data from 2217 BC patients who underwent SLN biopsy at Shantou University Medical College were analyzed, with 634 having positive SLNs. Patients were categorized into those with ≤ 2 positive SLNs and those with ≥ 3 positive SLNs. We applied nine ML algorithms to predict non-SLN metastasis. Model performance was evaluated using ROC curves, precision-recall curves, and calibration curves. Decision Curve Analysis (DCA) assessed the clinical utility of the models. RESULTS: The RF model showed superior predictive performance, achieving an AUC of 0.987 in the training set and 0.828 in the validation set. Key predictive features included size of positive SLNs, tumor size, number of SLNs, and ER status. In external validation, the RF model achieved an AUC of 0.870, demonstrating robust predictive capabilities. CONCLUSION: The developed RF model accurately predicts non-SLN metastasis in BC patients with ≥ 3 positive SLNs, suggesting that ALND might be avoided in selected patients by applying additional axillary radiotherapy. This approach could reduce the incidence of postoperative complications and improve patient quality of life. Further validation in prospective clinical trials is warranted.

SnO2QDs sensitized ZnFe2O4spheres with enhanced acetone sensing performance.

Herein, SnO2QDs (<10 nm) with small size instead of conventional nanoparticles was employed to modify ZnFe2O4to synthesize porous and heterogeneous SnO2/ZnFe2O4(ZFSQ) composites for gas sensing. By an immersion process combined with calcination treatment, the resultant porous ZFSQ composites with different contents of SnO2QDs were obtained, and their sensing properties were investigated. Compared with bare ZnFe2O4and SnO2QDs, porous ZFSQ composites based-sensors showed much improved sensor response to acetone. For contrast, the sensor performance of ZFSQ composites was also compared with that of ZnFe2O4sphere modified by SnO2nanoparticles with different size. The porous ZFSQ composite with 5 wt% SnO2QDs (ZFSQ-5) showed a better acetone sensing response than that of other ZFSQ composites, and it exhibited a high response value of 110-100 ppm of acetone and a low detection limit of 0.3 ppm at 240 °C. In addition to the rich heterojunctions and porous structure, the size effect of SnO2QDs was other indispensable reasons for the improved sensor performance. Finally, the ZFSQ-5 composite sensor was attempted to be applied for acetone sensing in exhaled breath, suggesting its great potential in monitoring acetone.

Comprehensive Analysis of the Associations of LOXL1-4 with Prognosis and Immune Infiltration in Breast Cancer.

Objective: Invasive breast cancer (BRCA) poses a major challenge to women's health due to its high incidence and poor prognosis. Dysregulated Lysine oxidase-like (LOXL) family genes are implicated in tumor progression across malignancies. Understanding the role of Lysine oxidase-like (LOXL) family genes in BRCA is crucial for advancing treatment strategies. Methods: TIMER, Oncomine, TNMplot, TCGA, GTEx and GEPIA datasets were used to investigate LOXL1-4 expression in breast cancer. The UALCAN and HPA datasets were utilized to detect the protein levels of LOXL1-4 in BRCA. Kaplan-Meier Plotter was used to analyze the prognostic values of LOXL1-4 in BRCA patients. Gene ontology (GO) and KEGG pathway enrichment analyses, conducted through DAVID 6.8 and R, revealed potential biological functions. TIMER was used to explore the link between LOXL1-4 expression and tumor immune infiltration. The cBioPortal dataset was used to analyze LOXL1-4 alterations and CNV-survival links in breast cancer. GSCA was used to assess LOXL1-4's correlations with immune infiltration. LOXL1-4's links to the eight immune checkpoint genes were analyzed using R's pheatmap. Results: Our study revealed that aberrant expression of LOXL1/2/4 in BRCA significantly affects relapse-free survival (RFS), overall survival (OS), and distant metastasis-free survival (DMFS), particularly highlighting the prognostic importance of LOXL4. LOXL1-4 displayed substantial relationships with the tumor immune microenvironment and immune cell infiltration. Furthermore, copy number variations (CNVs) of LOXL1-4 are significantly associated with immune infiltration in BRCA, particularly LOXL2 CNV, which significantly impacts OS and progression-free survival (PFS). Conclusion: The correlation between LOXL1-4 expression, prognosis, and immune infiltration in BRCA underscores their potential as biomarkers for prognosis and targets for immunotherapy.

Visual and Rapid Detection of Nerve Agent Mimics in Gas and Solution Phase by a Simple Fluorescent Probe.

Chemical nerve agents are highly toxic organophosphorus compounds that are easy to obtain and can be utilized by terrorists to threaten homeland security and human safety. Those organophosphorus nerve agents contain nucleophilic ability that can react with acetylcholinesterase leading to muscular paralysis and human death. Therefore, there is great importance to explore a reliable and simple method to detect chemical nerve agents. Herein, the o-phenylenediamine-linked dansyl chloride as a colorimetric and fluorescent probe has been prepared to detect specific chemical nerve agent stimulants in the solution and vapor phase. The o-phenylenediamine unit serves as a detection site that can react with diethyl chlorophosphate (DCP) in a rapid response within 2 min. A satisfied relationship line was obtained between fluorescent intensity and the concentration of DCP in the range of 0-90 µM. In the optimized conditions, we conducted the fluorescent titration to measure the limits of detection (0.082 µM) with the fluorescent enhancement up to 18-fold. Fluorescence titration and NMR studies were also conducted to explore the detection mechanism, indicating that the formation of phosphate ester causes the intensity of fluorescent change during the PET process. Finally, probe 1 coated with the paper test is utilized to detect DCP vapor and solution by the naked eye. We expect that this probe may give some admiration to design the small molecule organic probe and applied in the selectivity detection of chemical nerve agents.

Flexible Synergistic MoS2 Quantum Dots/PEDOT: PSS Film Sensor for Acetaldehyde Sensing at Room Temperature.

Acetaldehyde (CH3CHO) is known as a primary carcinogen, and the development of wearable gas sensors for its detection at room temperature has rarely been rarely reported. Herein, MoS2 quantum dots (MoS2 QDs) have been employed to dope with poly(3,4-ethylenedioxythiophene): polystyrenesulfonate (PEDOT: PSS) via a simple in situ polymerization technique, and the CH3CHO gas-sensing properties of the resultant flexible and transparent film were investigated. MoS2 QDs had been evenly dispersed into the polymer, and it was shown that PEDOT: PSS doped with the 20 wt % MoS2 QDs sensor exhibited the highest response value of 78.8% against 100 ppm CH3CHO and its detection limit reached 1 ppm. Moreover, the sensor response remained stable for more than 3 months. In particular, the different bending angles (from 60 to 240°) had little effect on the sensor response to CH3CHO. The possible reason for the enhanced sensing properties was attributed to the large number of reaction sites on the MoS2 QDs and the direct charge transfer between the MoS2 QDs and PEDOT: PSS. This work suggested a platform to inspire MoS2 QDs-doping PEDOT: PSS materials as wearable gas sensors for highly sensitive chemoresistive sensors to detect CH3CHO at room temperature.

Expression of CD22 in Triple-Negative Breast Cancer: A Novel Prognostic Biomarker and Potential Target for CAR Therapy.

Triple-negative breast cancer (TNBC) accounts for 15-20% of all breast cancer cases. Due to the lack of expression of well-known molecular targets [estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2)], there is a need for more alternative treatment approaches in TNBC. Chimeric antigen receptor (CAR)-T cell-based immunotherapy treatment is one of the latest treatment technologies with outstanding therapeutic advances in the past decade, especially in the treatment of hematologic malignancies, but the therapeutic effects of CAR-T cells against solid tumors have not yet shown significant clinical benefits. Identification of highly specific CAR-T targets in solid tumors is also crucial for its successful treatment. CD22 is reported to be a multifunctional receptor that is mainly expressed on the surface of mature B-cells (lymphocytes) and is also highly expressed in most B-cell malignancies. This study aimed to investigate the expression of CD22 in TNBC. Bioinformatic analysis was performed to evaluate the expression of CD22 in breast carcinoma and normal tissues. RNA-seq data of normal and breast carcinoma patients were downloaded from The Cancer Genome Atlas (TCGA), and differential gene expression was performed using R language. Additionally, online bioinformatics web tools (GEPIA and TNM plot) were used to evaluate the expression of CD22 in breast carcinoma and normal tissues. Western blot (WB) analysis and immunofluorescence (IF) were performed to characterize the expression of CD22 in TNBC cell lines. Immunohistochemical (IHC) staining was performed on tumor specimens from 97 TNBC patients for CD22 expression. Moreover, statistical analysis was performed to analyze the association of clinical pathological parameters with CD22 expression. Correlation analysis between overall survival data of TNBC patients and CD22 expression was also performed. Differential gene expression analysis of TCGA data revealed that CD22 is among the upregulated differentially expressed genes (DEGs) with high expression in breast cancer, as compared to normal breast tissues. WB and IF analysis revealed high expression of CD22 in TNBC cell lines. IHC results also showed that approximately 62.89% (61/97) of TNBC specimens were stained positive for CD22. Cell membrane expression of CD22 was evident in 23.71% (23/97) of TNBC specimens, and 39.18% (38/97) of TNBC specimens showed cytoplasmic/membrane expression, while 37.11% (36/97) specimens were negative for CD22. Furthermore, significant associations were found between the size of tumors in TNBC patients and CD22 expression, which unveils its potential as a prognostic biomarker. No significant correlation was found between the overall survival of TNBC patients and CD22 expression. In conclusion, we demonstrated for the first time that CD22 is highly expressed in TNBC. Based on our findings, we anticipated that CD22 could be used as a prognostic biomarker in TNBC, and it might be a potential CAR-T target in TNBC for whom few therapeutic options exist. However, more large-scale studies and clinical trials will ensure its potential usefulness as a CAR-T target in TNBC.

[Clinical Study of San Wei Sheng Huo Decoction in the Treatment of Refractory Chemotherapy-Induced Thrombocytopenia].

Objective: To investigate the efficacy and safety of treating refractory chemotherapy-induced thrombocytopenia (RCIT) with San Wei Sheng Huo Decoction (SWSHD) as the main formula. Methods: A retrospective study was conducted and the data of RCIT patients treated with SWSHD as the main formula were collected. Changes in peripheral blood platelet (PLT) levels at different time points of treatment were examined and the significant effective rate (SER) and effective rate (ER) were analyzed. We measured the increase in peripheral blood PLT count before and after treatment, analyzed the differences in PLT count increase for different degrees of RCIT treatment, and evaluated the safety of the treatment. Results: A total of 35 cases of RCIT were included in the study. With SWSHD as the main treatment formula, the 2-week ER and SER were 74.29% and 14.29%, respectively, the 2-month ER and SER were 84.38% and 60.50, respectively, and the 1-year ER and SER were 92.31% and 80.77%, respectively. PLT count increased at all time points after treatment compared with that before treatment ( P<0.01). Subgroup analysis showed that, 2 months after treatment started, peripheral blood PLT counts increased by as much as 51.02×10 9L －1 in the severe RCIT group, higher than that of the moderate RCIT group at 36.58×10 9L －1 ( P<0.05), and the difference persisted until 1 year after the treatment. No obvious traditional Chinese medicine-related adverse reaction was observed during the treatment. Conclusion: SWSHD takes effect rapidly and its effect is long-lasting and stable. Furthermore, SWSHD has a more significant effect on severe RCIT.

Glis2 inhibits the epithelial-mesenchymal transition and apoptosis of renal tubule cells by regulating the ß-catenin signalling pathway in diabetic kidney disease.

Increasing evidence has supported the idea that epithelial-to-mesenchymal transition (EMT)-based tubulointerstitial fibrosis and the apoptosis of renal tubular epithelial cells (TECs) play important roles in the occurrence and development of Diabetic kidney disease (DKD). Glis2 is abundantly expressed in renal tubules and is a member of the Kruppel-like zinc finger transcription factor family, which is involved in the regulation of normal renal development and function. Glis2 deficiency may be closely associated with tubular atrophy and fibrosis, but the role played by Glis2 in DKD remains unclear. In this study, we found that Glis2 protein expression was downregulated in kidney tissue samples obtained by biopsy from DKD patients as well as HK-2 cells cultured in high-glucose medium, and overexpression of the Glis2 plasmid inhibited the apoptosis and EMT of TECS under HG conditions. In addition, Glis2 overexpression obliterated the activation of the ß-catenin signalling pathway in HG-cultured HK-2 cells. Moreover, the ß-catenin inhibitor XAV939 or XAV939 combined with Glis2 overexpression markedly inhibited the apoptosis and EMT of HG-treated HK-2 cells. All these findings indicated that upregulation of Glis2 expression might attenuate the EMT and apoptosis of renal tubule cells via the ß-catenin signalling pathway under HG conditions. This outcome may lead to a better understanding of the pathogenesis of DKD and provide new insights into prevention and treatment strategies targeting DKD.

[Meta-analysis of efficacy and safety of Hulisan Capsules in treatment of knee osteoarthritis].

This study aims to assess the efficacy and safety of Hulisan Capsules in the treatment of knee osteoarthritis, which is expected to serve as a reference for clinical practice. To be specific, randomized controlled trial(RCT) on the treatment of knee osteoarthritis with Hulisan Capsules was retrieved from EMbase, PubMed, Cochrane Library, Web of Science, CNKI, Wanfang, SinoMed, and VIP(from inception to November 15, 2021). Two researchers independently screened the articles, extracted the data, and evaluated the risk of bias with ROB. RevMan 5.4 was used for Meta-analysis. Finally, 12 RCTs were screened out, involving 1 703 cases(1 075 in the experimental group and 628 in the control group). Meta-analysis showed that conventional treatment + Hulisan Capsules was superior to conventional treatment alone in terms of symptom relief rate(RR=1.19, 95%CI[1.09, 1.30], P<0.000 1), Lysholm score(MD=11.17, 95%CI[7.35, 15.00], P<0.000 01), visual analogue scale(VAS) score(MD=-0.99, 95%CI[-1.30,-0.68], P<0.000 01), and knee function score(RR=8.94, 95%CI[6.51, 11.37], P<0.000 01). Hulisan Capsules alone was superior to the conventional treatment alone in terms of the symptom relief rate(RR=1.38, 95%CI[1.13, 1.69], P=0.002) and knee function score(MD=2.88, 95%CI[0.81, 4.94], P=0.006), but VAS score was insignificantly different between the patients treated with Hulisan Capsules alone and those with conventional treatment alone(MD=-0.57, 95%CI[-1.42, 0.29], P=0.19). Hulisan Capsules + conventional treatment showed insignificant difference in symptom relief rate from the Zhuifeng Tougu Capsules + conventional treatment(RR=1.07, 95%CI[0.91, 1.25], P=0.44). The Lequesne score was insignificantly different between Hulisan Capsules + conventional treatment and conventional treatment/Zhuifeng Tougu Capsules + conventional treatment(MD=-2.17, 95%CI[-6.29, 1.96], P=0.30). The incidence of adverse reactions in the experimental group was significantly lower than control group(RR=0.57, 95%CI[0.34, 0.96], P=0.03). According to the available data and methods, Hulisan Capsules/Hulisan Capsules + conventional treatment could improve the symptom relief rate, Lysholm score, knee function score, and VAS score of patients with knee osteoarthritis, and alleviate the symptoms of pain, stiffness, and swelling of them. No serious adverse reactions were found yet. In the future, more large-sample and standard clinical trials are needed to verify the effect and safety of Hulisan Capsules in the treatment of knee osteoarthritis.

A Multitargeted Electrochemiluminescent Biosensor Coupling DNAzyme with Cascading Amplification for Analyzing Myocardial miRNAs.

Several circulating miRNAs are associated with the pathogenic process of acute myocardial infarction (AMI). Thus, analyzing myocardial miRNAs in the circulatory system is important for the diagnosis and treatment of AMI, especially for early-stage diagnosis. Based on the characteristics of myocardial miRNAs, an ultrasensitive and multitargeted electrochemiluminescence (ECL) sensing platform was developed with a versatile probe that can couple DNAzyme with hybridization chain reaction amplification. The target miRNA and auxiliary chains form a circular unit that shears the versatile probe hairpin, and the products subsequently trigger cascading amplification; a long strand of dsDNA is then generated with many C-rich sequences that can undergo in situ reductions to generate ECL luminophore silver clusters. Using this strategy, three myocardial miRNAs are successfully detected with a detection limit as low as 29.6 aM (S/N = 3). Notably, our method can detect myocardial miRNA groups composed of multiple related circulating miRNAs with high selectivity over interfering miRNAs in blood. This is extremely important for solving the problem of diverse and low abundance of infarct-associated miRNAs. Our strategy pioneers a new idea of miRNA detection, and given its versatility and sensitivity, it is promising for the diagnosis of multigene-regulated cardiovascular diseases.