Non-diabetic elderly populations: the MHR as a protective factor against bone abnormalities.

Objectives: In China, osteoporosis has become a major health concern among elderly population, imposing significant burden on the country's social and economic systems. The monocyte to high-density lipoprotein ratio (MHR) has been currently recommended as a novel marker of inflammation and oxidative stress associated with osteoporosis in type 2 diabetes mellitus (T2DM). However, its reliability in non-diabetic elderly populations remains unclear. The present study was to evaluate the association between MHR and osteoporosis in a non-diabetic elderly population. Methods: The clinical data of 240 non-diabetic elderly subjects (115 in the osteoporosis group and 125 in the normal bone group) were retrospectively analyzed and all statistical analyses were performed by using SPSS 26.0. Results: Differences in age, neutrophils, lymphocytes, monocytes, MHR, uric acid, creatinine, triglycerides,and high-density lipoprotein cholesterol were found to be statistically significant between the two groups. A binary logistic regression model was conducted by including age, MHR, UA and Cr as variables. The results showed that age was an independent risk factor and MHR was an independent protective factor for bone abnormality in the non-diabetic elderly population. The ROC analysis showed that the area under the curve for the predictive effect of MHR, age and their combined test on osteoporosis in non-diabetic elderly populations was 0.623, 0.728 and 0.761, respectively; the correlation analysis showed that MHR was positively correlated with lumbar and hip BMD, and negatively associated with femoral neck stress ratio, femoral intertrochanteric stress ratio, and femoral stem stress ratio, showing statistically significant differences (P<0.05). Conclusions: For the non-diabetic elderly population: the MHR is a protective factor against bone abnormalities and was significantly higher in the normal bone group than in the abnormal bone group.

Long-term overall survival of patients who undergo breast-conserving therapy or mastectomy for early operable HER2-Positive breast cancer after preoperative systemic therapy: an observational cohort study.

Background: Understanding the survival outcomes associated with breast-conserving therapy (BCT) and mastectomy after preoperative systemic therapy (PST) enables clinicians to provide more personalized treatment recommendations. However, lack of firm survival benefit data limits the breast surgery choices of human epidermal growth factor receptor 2 (HER2)-positive breast cancer patients who receive PST. We sought to determine whether BCT or mastectomy after PST for early operable HER2-positive breast cancer is associated with better long-term survival outcomes and determine the degree to which PST response affects this association. Methods: In this observational cohort study, we compared the long-term survival outcomes of BCT and mastectomy after PST for HER2-positive breast cancer and evaluated the impact of PST response on the relationship between breast surgery performed and survival outcomes. Our cohort included 625 patients with early operable HER2-positive breast cancer who received PST followed by BCT or mastectomy between January 1998 and October 2009. These patients also received standard postoperative radiation, trastuzumab, and endocrine therapy as indicated clinically. We used propensity score matching to assemble mastectomy and BCT cohorts with similar baseline characteristics and used Kaplan-Meier plots and Cox proportional hazards regression to detect associations between surgery types and outcomes. Furthermore, in this study, we analyzed the original data of 625 patients using the inverse probability of treatment weighting (IPTW) method to enhance the reliability of the comparison between the mastectomy and BCT cohorts by addressing potential confounding variables. Findings: Propensity score matching yielded cohorts of 221 patients who received BCT and 221 patients who underwent mastectomy. At the median follow-up time of 9.9 years, compared with BCT, mastectomy was associated with worse overall survival (hazard ratio, 1.66; 95% confidence interval [CI]: 1.08-2.57; P = 0.02). In patients who had axillary lymph node pathological complete response, mastectomy was associated with worse overall survival before matching (hazard ratio, 2.17; 95% CI: 1.22-3.86; P < 0.01) and after matching (hazard ratio, 2.12; 95% CI: 1.15-3.89; P = 0.02). Among patients with pathological complete response in the breast, the survival results did not differ significantly between BCT and mastectomy patients. IPTW method validated that BCT offers better overall survival in patients who had axillary lymph node pathological complete response. Interpretation: People with HER2-positive breast cancer who have already had PST are more likely to survive after BCT, especially if they get a pathological complete response in the axillary lymph nodes. These findings underscore the necessity for further investigation into how responses to PST can inform the choice of surgical intervention and the potential impact on overall survival. Such insights could lead to the development of innovative tools that support personalized surgical strategies in the management of breast cancer. Funding: This work was supported by grants from the Nantong Science and Technology Project (JCZ2022079), Nantong Health Commission Project (QA2021031, MSZ2023040) and National Natural Science Foundation of China (No. 82394430).

Survival impact of gastrectomy and chemotherapy on gastric signet ring-cell carcinoma with different metastatic lesions: A population-based study.

BACKGROUND: A comprehensive understanding of gastric signet ring cell carcinoma (SRCC) is limited. The aim of our study was to analyze metastatic patterns of gastric SRCC and evaluate impacts of gastrectomy and chemotherapy for metastatic gastric SRCC. METHODS: We obtained data of gastric cancer patients between 2010 and 2017 in the Surveillance, Epidemiology, and End Results database. Chi-square tests were used to compare data significance. Kaplan-Meier, Cox proportional hazards regression and Fine-Gray competing risk analysis were used to analyze the difference in the overall survival (OS) and cancer-specific survival (CSS). Propensity-score matching was used to adjust numerical difference. RESULTS: Among 36,459 eligible gastric cancer patients, 6264 (17.2 %) were SRCC patients. Bone metastasis was more common in SRCC patients than in non-SRCC patients. The multivariate analysis showed that chemotherapy (HR = 0.30, 95 %CI = 0.27-0.33, p < 0.01) and gastrectomy (HR = 0.51, 95 %CI = 0.45-0.59, p < 0.01) were protective prognostic factors in certain stage Ⅳ SRCC patients. For the effect of gastrectomy, survival benefits could be found in patients with liver metastasis. The gastrectomy was not associated with improved OS in patients with lung or multiple metastases. In subgroup analysis, SRCC patients with metastasis who received gastrectomy and chemotherapy (HR = 0.17, p < 0.01; HR = 0.03, p < 0.01) had a better OS and CSS than those who had chemotherapy only (HR = 0.30, p < 0.01; HR = 0.18, p < 0.01). CONCLUSION: Our study analyzed the unique metastatic patterns of gastric SRCC and recommended chemotherapy as the first choice in metastatic SRCC. For patients with liver metastasis, gastrectomy plus chemotherapy can be considered.

Slit Guidance Ligand 3 (SLIT3) Loaded in Hydrogel Microparticles Enhances the Tendon-Bone Healing through Promotion of Type-H Vessel Formation: An Experimental Study in Mice.

Poor tendon-bone interface (TBI) integration is one of the major causes contributing to unsatisfactory healing quality in patients after anterior cruciate ligament (ACL) reconstruction. Type H vessels have been recently found to closely modulate bone formation via regulation of the osteo-angiogenic crosstalk, so the strategies favoring type H vessel formation may be promising therapeutic approaches for improved graft osteointegration. In this study, we reported for the first time the treatment outcome of slit guidance ligand 3 (slit3), a novel proangiogenic factor favoring type H vessel formation, in TBI healing in mice with ACL reconstruction. The mice (n = 87) were divided into three groups for various treatments: hydrogel microparticles (HMP, control group), slit3@HMP, and slit3 neutralizing antibody@HMP (slit3-AB@HMP). Histological analysis, gait performance, radiographic measurement, and biomechanical testing were performed to assess the TBI healing quality. Increased bony ingrowth and reduced fibrous scar tissue was formed at the TBI in the slit3@HMP group when compared to the HMP group. Meanwhile, the slit3-AB@HMP inhibited the osseous ingrowth and increased fibrous scar tissue formation relative to the HMP group. Compared to the HMP group, the slit3@HMP favored type H vessel formation at the TBI while the slit3-AB@HMP impeded it. According to micro-CT assessment, compared to the HMP group, the slit3@HMP significantly increased the peri-tunnel bone mass while the slit3-AB@HMP significantly reduced the peri-tunnel bone mass. The mice in the slit3@HMP group showed the best gait performance in terms of stance time, stride length, paw print area, and stance pressure. Dynamic laxity measurement and tensile testing showed the slit3@HMP group exhibited significantly reduced laxity displacement and improved failure load and stiffness relative to the other two groups. Collectively, the injection of slit3 could be used to enhance tendon-bone integration, which may be ascribed to modulation of angiogenesis-osteogenesis crosstalk coupled by type H vessels.

Bronchoscopic treatment of multiple bronchial myelolipomas: a case report and literature review.

BACKGROUND: Extra-adrenal myelolipoma is an unusual entity, and endobronchial myelolipoma is rarer, which is often ignored by clinicians, delaying the disease and affecting the prognosis. CASE PRESENTATION: A 71-year-old man with a history of chronic obstructive pulmonary disease (COPD) and type 2 diabetes mellitus, with recurrent fever, cough, and expectoration for more than 2 weeks experienced relief in cough, phlegm reduction, and glycemic control with anti-inflammatory treatment. Further examination revealed that new growths obstructing all lobar bronchi impaired flexible bronchoscope entry. In order to relieve the patient's symptoms, under general anesthesia, we performed liquid nitrogen cryobiopsy at multiple bronchial openings, and then used argon plasma coagulation (APC) to achieve hemostasis. The pathological diagnosis was bronchial myelolipoma. The largest volume of the resected tissue was a mass measuring 0.6 cm × 0.4 cm × 0.3 cm at the bronchial opening of the upper lobe of the left lung. The patient's condition was stable and the symptoms were partially relieved after surgery. No recurrence was observed during the 12-month follow-up, although the long-term treatment efficacy is unknown. CONCLUSION: Pathological biopsy is key to the diagnosis of endobronchial myelolipoma, and the development of the endobronchial myelolipomas may have been associated with long-term poor control of steroid levels in this patient.

Effects of microplastics in aquatic environments on inflammatory bowel disease.

The incidence of inflammatory bowel disease (IBD) has been increasing in recent years, particularly in newly industrialized nations. Environmental factors have been identified as playing a crucial role in IBD pathogenesis. Microplastics (MPs), a novel class of environmental pollutants, are a significant global pollution concern. MPs are found in almost all aquatic environments. MPs in the environment may pose health risks, specifically concerning the intestinal system, due to prolonged exposure through the consumption of aquatic foods and drinking water. In this review, we aimed to provide a comprehensive overview of the current knowledge on the impact of MPs in water resources on the occurrence and progression of IBD. Our systematic analysis of in vitro and in vivo studies found that MPs induce intestinal barrier dysfunction, imbalance in the intestinal microbiome, and metabolic abnormalities, ultimately leading to IBD. In addition, MP exposure causes greater harm to individuals with preexisting gastrointestinal disorders than those without them. Our analysis of this literature review highlights the need for further research to improve the understanding of the complex relationship between MP exposure and IBD.

A new inhibitor of human peptide deformylase suppresses cell proliferation and induces cell apoptosis and autophagy in cancers.

Human peptide deformylase (hsPDF) has been found overexpressed in many cancer cells and its inhibitors exhibit antitumor activity. Studies were performed to validate that hsPDF is a good antitumor target. The inhibitory effect of PDF64 on hsPDF enzymatic activity was measured and confirmed by computation analysis. Antiproliferation activity was determined and in-vivo antitumor activity were analyzed in HCT116 and HL60 nude mice xenografts. Mitochondrial membrane potential (MMP), cell apoptosis, and autophagic cell death were analyzed by flow cytometry. ATP level was quantified using an ATP assay kit. Protein expression and kinase phosphorylation were determined by western blotting. A new hsPDF inhibitor PDF64 was identified. It showed evident antiproliferation activity in 10 cancer cells and significantly suppressed tumor growth in HCT116 and HL60 xenografts. It induced an obvious decrease in MMP and caused apparent cell apoptosis and autophagy in HCT116 and Jurkat cells. PDF64 treatment also led to an evident decrease in cellular ATP levels in these cells. Moreover, PDF64 downregulated c-Myc expression and had some effects on extracellular regulated protein kinases (ERK) and protein kinase B (Akt)/ mammalian target of rapamycin (mTOR) pathways. PDF64 exhibited good antitumor effects both in vivo and in vitro . It caused cell apoptosis and autophagic death in HCT116 and Jurkat cells. The effects may be mediated by inhibiting c-Myc expression and ERK or PI3K-Akt-mTOR pathway. Therefore, PDF64 may be a promising reagent for antitumor drug development, which further supports that hsPDF is a good antitumor drug target.

Essential oils as natural antimicrobials applied in meat and meat products-a review.

Meat and meat products are highly susceptible to the growth of micro-organism and foodborne pathogens that leads to severe economic loss and health hazards. High consumption and a considerable waste of meat and meat products result in the demand for safe and efficient preservation methods. Instead of synthetic additives, the use of natural preservative materials represents an interest. Essential oils (EOs), as the all-natural and green-label trend attributing to remarkable biological potency, have been adopted for controlling the safety and quality of meat products. Some EOs, such as thyme, cinnamon, rosemary, and garlic, showed a strong antimicrobial activity individually and in combination. To eliminate or reduce the organoleptic defects of EOs in practical application, EOs encapsulation in wall materials can improve the stability and antimicrobial ability of EOs in meat products. In this review, meat deteriorations, antimicrobial capacity (components, effectiveness, and interactions), and mechanisms of EOs are reviewed, as well as the demonstration of using encapsulation for masking intense aroma and conducting control release is presented. The use of EOs individually or in combination and encapsulated applications of EOs in meat and meat products are also discussed.

Elaiophylin Inhibits Tumorigenesis of Human Lung Adenocarcinoma by Inhibiting Mitophagy via Suppression of SIRT1/Nrf2 Signaling.

Lung adenocarcinoma (LADC), the most common type of lung cancer, is still one of the most aggressive and rapidly fatal tumor types, even though achievements in new therapeutic approaches have been developed. Elaiophylin as a C2 symmetrically glycosylated 16 macrolides has been reported to be a late-stage autophagy inhibitor with a potent anti-tumor effect on various cancers. This study investigated the anti-tumor effect of elaiophylin on human LADC for the first time in in vitro and in vivo models. The in vitro study in LADC A549 cells showed that elaiophylin significantly inhibited cell viability and induced cell apoptosis through the suppression of mitophagy and induction of cellular and mitochondrial oxidative stress. Proteomic analysis and molecular docking assay implicated that SIRT1 was likely the direct target of elaiophylin in A549 cells. Further mechanistic study verified that elaiophylin reduced Nrf2 deacetylation, expression, and transcriptional activity as well as cytoplasm translocation by downregulating SIRT1 expression and deacetylase activity. Additionally, SIRT1/Nrf2 activation could attenuate elaiophylin-induced mitophagy inhibition and oxidative stress. The in vivo study in the A549-xenograft mice model showed that the anti-tumor effect of elaiophylin was accompanied by the decreased expressions of SIRT1, Nrf2, Parkin, and PINK1. Thus, the present study reports that elaiophylin has potent anti-tumor properties in LADC, which effect is likely mediated through suppressing the SIRT1/Nrf2 signaling. In conclusion, elaiophylin may be a novel drug candidate for LADC and SIRT1 may be a new therapeutic target for such devastating malignancy.

Erdafitinib Inhibits Tumorigenesis of Human Lung Adenocarcinoma A549 by Inducing S-Phase Cell-Cycle Arrest as a CDK2 Inhibitor.

Lung adenocarcinoma (LADC) is the most prevalent lung cancer sub-type, and targeted therapy developed in recent years has made progress in its treatment. Erdafitinib, a potent and selective pan-FGFR tyrosine kinase inhibitor, has been confirmed to be effective for the treatment of LADC; however, the molecular mechanism responsible for this effect is unclear. The in vitro study showed that erdafitinib exhibited an outstanding anti-cancer activity in human LADC cell line A549 by inducing S-phase cell-cycle arrest and cell apoptosis. The mechanistic study based on the transcriptomic data revealed that erdafitinib exerted its anti-cancer effect by affecting the cell cycle-related pathway, and CDK2 was the regulatory target of this drug. In addition, CDK2 overexpression significantly attenuated the anti-cancer effect of erdafitinib by affecting the transcriptional activity and expression of E2F1, as well as the expression of CDK1. The in vivo study showed that erdafitinib presented an obvious anti-cancer effect in the A549 xenograft mice model, which was accompanied by the reduced expression of CDK2. Thus, this study demonstrates the anti-cancer effect of erdafitinib against LADC for the first time based on in vitro and in vivo models, whose activity is achieved by targeting CDK2 and regulating downstream E2F1-CDK1 signaling. This study may be helpful for expanding the clinical application of erdafitinib in treating LADC.

Analysis of m6A-related signatures associated with the tumor immune microenvironment and predict survival in acute myeloid leukemia.

Background: Most previous studies have focused on the intrinsic carcinogenic pathways of tumors; however, little is known about the potential role of N6-methyladenosine (m6A) methylation in the tumor immune microenvironment (TIME). To better diagnose and treat acute myeloid leukemia (AML), we sought to examine the correlation between m6A regulatory factors and immune infiltration in cases of AML. At the same time, a prognostic model was constructed to predict the survival of AML. Methods: We extracted data from The Cancer Genome Atlas (TCGA) database, including ribonucleic acid sequencing (RNA-seq) transcriptome data and data on the corresponding clinical characteristics of AML patients. We identified two m6A modification patterns with distinct clinical outcomes and found a significant relationship between them. Simultaneous discovery of distinct m6A clusters associated with the tumor immune microenvironment [immune cell types and Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data (ESTIMATE) algorithm] are closely related. Next, we implemented Lasso (Least Absolute Shrinkage and Selection Operator) Cox regression to build a predictive model in the 2-m6A regulator TCGA dataset to further explore m6A prognostic features in AML, and perform correlation validation. Results: We identified 2 molecular subtypes (Clusters 1 and 2) by the consistent clustering of significant m6A regulators in AML. Cluster 2 was associated with a higher immune score and obvious immune cell infiltration, and thus patients in Cluster 2 had a poorer prognosis than those in Cluster 1 (P<0.05). Additionally, the 2 m6A-related signatures representing the independent prognostic factors in AML were screened to construct a prognostic risk-score model. We found that patients with low-risk scores had higher immune scores than those with high-risk scores (P<0.05). Conclusions: Our research confirmed that m6A methylation plays an important role in AML. Further provide new directions for the prognosis and treatment of AML.

Bit1 is involved in regulation between integrin and TGFß signaling in lens epithelial cells.

Bit1, as an integrin-specific effector, is specifically expressed in lens epithelial cells (LECs) and may be essential to maintain the normal function of LECs. The present study investigated the function of Bit1 and its regulatory mechanism in LECs. Knockdown of Bit1 was mediated by a lentivirus with a specific short-hairpin RNA against Bit1 in SRA01/04 cells. Cell proliferation ability was measured by CCK-8 assay. Cell migration was examined by transwell and wound-healing assays. The effect of Bit1 knockdown on genome-wide expression patterns was studied via a GeneChip® PrimeView™ Human Gene Expression Array. Based on the ingenuity pathway analysis (IPA), Bit1's regulation of target pathways and genes was verified by real-time qPCR and Western blotting. Bit1 knockdown inhibited proliferation, migration, and regulated cell cycle and apoptosis of LECs. Microarray gene expression analysis and IPA assays revealed that integrin and TGFß signaling pathways were remarkably impacted by Bit1 expression. FAK, PAK2, ITGA5, and ITGB1 were identified as core node molecules under the control of Bit1. Bit1 participates in integrin and TGFß signaling via regulating downstream FAK and PAK2 and subsequently affecting EMT-related gene expression including ITGA5, ITGB1, and αSMA. In conclusion, Bit1 plays as an important role in the regulation between integrin and TGFß signaling, which affects cell survival, migration, and EMT of LECs.

Elaiophylin Inhibits Tumorigenesis of Human Uveal Melanoma by Suppressing Mitophagy and Inducing Oxidative Stress via Modulating SIRT1/FoxO3a Signaling.

Uveal melanoma (UM) is the most common primary intraocular tumor in adults, which is associated with poor prognosis. Up to 50% of UM patients develop metastasis. Therapeutics that have proven effective in cutaneous melanoma have little success in treating UM, possibly due to its low mutational burden. Therefore, new drug therapies are highly desired for UM. Our in vitro studies showed that Elaiophylin, a late-stage autophagy inhibitor, exhibited an outstanding anticancer activity in human UM cell lines and human UM primary cells through suppressing mitophagy, inducing oxidative stress and leading to autophagic cell death. Our mechanistic study revealed that Elaiophylin exerted its effect by down-regulating SIRT1 and thus influencing deacetylation and mitochondrial localization of FoxO3a. In our confirmatory experiments, SRT1720, a SIRT1 specific activator, could attenuate Elaiophylin-induced inhibition of mitophagy and elevation of oxidative stress, and such effects was partly reversed by FoxO3a knockdown. Our further in vivo studies showed that Elaiophylin dramatically inhibited tumor growth in the human UM xenograft mouse model, which was accompanied with a decreased SIRT1 expression. Thus, the current study is the first to demonstrate that Elaiophylin has a potent anti-cancer effect against UM, which activity is possibly mediated through regulating SIRT1-FoxO3a signaling axis. And Elaiophylin may be a new and promising drug candidate to treat human UM.

Breast-conserving therapy is associated with better survival than mastectomy in Early-stage breast cancer: A propensity score analysis.

BACKGROUND: Recent retrospective studies have reported that breast-conserving therapy (BCT) led to improved overall survival (OS) than mastectomy in some populations. We aimed to compare the efficacy of BCT and mastectomy using the SEER database. MATERIALS AND METHODS: Between 2010 and 2015, 99,790 eligible patients were identified. We included early-stage breast cancer patients with 5cm or smaller tumors and three or fewer positive lymph nodes in our study. We compared the OS and breast cancer-specific survival (BCSS) results among patients with BCT and those with mastectomy. Kaplan-Meier plots, Cox proportional hazard regressions, competing risk analysis, and multivariate regressions were used to evaluate the outcomes. Propensity-score matching was used to assemble a cohort of patients with similar baseline characteristics. RESULTS: In our study, 77,452 (77.6%) patients underwent BCT and 22,338 (22.4%) underwent mastectomy. The 5-year OS rate was 94.7% in the BCT group and 87.6% in the mastectomy group, and the 5-year BCSS was 97.2% in the BCT and 94.3% in the mastectomy group. Multivariate analysis in the matched cohort showed that women underwent mastectomy was associated with worse OS (Hazard ratio (HR) = 1.79; 95% confidence intervals (CIs) = 1.59-2.02, p < 0.001) and BCSS (HR = 1.88; 95% CIs = 1.61-2.18, p < 0.001) results compared with those underwent BCT. Patients with different subtypes and age group (>50 years old; ≤50 years old) received BCT showed significantly better OS and BCSS results than those received mastectomy. The effect of surgery choice on survival yielded similar results either for all patients or matched cohorts. CONCLUSIONS: Our study showed that BCT was associated with improved survival compared with mastectomy in early-stage breast cancer patients. It seems advisable to encourage patients to receive BCT rather than mastectomy in early-stage patients when feasible and appropriate.

Nine-Year Median Follow-up of Cardiotoxicity and Efficacy of Trastuzumab Concurrently With Anthracycline-Based and Anthracycline-Free Neoadjuvant Chemotherapy in HER2-Positive Breast Cancer Patients.

BACKGROUND: The combination of trastuzumab with anthracycline chemotherapy drugs is associated with synergistic cardiotoxicity. The aim of this study is to compare the efficacy and late-onset cardiac toxicity of neoadjuvant chemotherapy regimens, trastuzumab plus paclitaxel followed by 5-fluorouracil, epirubicin, and cyclophosphamide (PH-FECH) versus trastuzumab plus docetaxel and carboplatin (TCH), for human epidermal growth factor receptor 2-positive (HER2+) breast cancer (BC). METHODS: Patients with HER2+ BC who received neoadjuvant chemotherapy with PH-FECH or TCH between 2002 and 2009 at MD Anderson Cancer Center were included. The primary endpoint was progression-free survival (PFS). Secondary endpoints included pathological complete response (pCR), overall survival, cardiac events, breast cancer-specific survival, noncardiac toxicities, and chemotherapy interruption. RESULTS: We identified 249 consecutive patients (184 who received PH-FECH and 65 who received TCH). The 10-year PFS was higher in the PH-FECH group than in the TCH group (83.6% vs. 72.2%; P = .044). The pCR rate was significantly higher in the PH-FECH group (58.2% vs. 41.5%; P = .021). The rate of cardiac events was higher in the PH-FECH group, but the difference was not significant (13.0% vs. 7.7%; P = .352). More patients developed late-onset cardiotoxicity in the PH-FECH group (3.8%) than in the TCH group (1.5%). Hypertension (odds ratio, 4.402 [95% confidence interval, 1.020-18.998]; P = .047) was an independent predictor of late-onset cardiotoxicity. CONCLUSIONS: Both neoadjuvant regimens are effective and tolerable in patients with HER2+ BC. The PH-FECH regimen offers a higher pCR rate and higher PFS but no difference in overall survival or breast cancer-specific survival. Higher frequency of cardiac toxicity with PH-FECH was noted.

Pipette-Tip-Enabled Digital Nucleic Acid Analyzer for COVID-19 Testing with Isothermal Amplification.

Herein, a pipette-tip-enabled digital nucleic acid analyzer for high-performance COVID-19 testing is demonstrated. This is achieved by digital loop-mediated isothermal amplification (digital LAMP or dLAMP) using common laboratory equipment and materials. It is shown that simply fixing a glass capillary inside conventional pipette tips enables the generation of monodisperse, water-in-oil microdroplets with benchtop centrifugation. It is shown that using LAMP, the ORF1a/b gene, a standard test region for COVID-19 screening, can be amplified without a thermal cycler. The amplification allows counting of fluorescent microdroplets so that Poisson analysis can be performed to allow quantification with a limit of detection that is 1 order of magnitude better than those of nondigital techniques and comparable to those of commercial dLAMP platforms. It is envisioned that this work will inspire studies on ultrasensitive digital nucleic acid analyzers demanding both sensitivity and accessibility, which is pivotal to their large-scale applications.

Magnetically Enhanced Liquid SERS for Ultrasensitive Analysis of Bacterial and SARS-CoV-2 Biomarkers.

In this work, it is shown that surface-enhanced Raman scattering (SERS) measurements can be performed using liquid platforms to perform bioanalysis at sub-pM concentrations. Using magnetic enrichment with gold-coated magnetic nanoparticles, the high sensitivity was verified with nucleic acid and protein targets. The former was performed with a DNA fragment associated with the bacteria Staphylococcus aureus, and the latter using IgG antibody, a biomarker for COVID-19 screening. It is anticipated that this work will inspire studies on ultrasensitive SERS analyzers suitable for large-scale applications, which is particularly important for in vitro diagnostics and environmental studies.

Exploring the Clinical Utility of Metagenomic Next-Generation Sequencing in the Diagnosis of Pulmonary Infection.

INTRODUCTION: We aimed to explore the real-world clinical application value and challenges of metagenomic next-generation sequencing (mNGS) for pulmonary infection diagnosis. METHODS: We retrospectively reviewed the results of mNGS and conventional tests from 140 hospitalized patients with suspected pulmonary infections from January 2019 to December 2020. The sample types included bronchoalveolar lavage fluid, lung tissue by transbronchial lung biopsy, pleural effusion, blood, and bronchial sputum. Apart from the mNGS reports that our patients received, an extra comprehensive and thorough literature search was conducted. RESULTS: Significant differences were noticed in the positive detection rates of pathogens between mNGS and conventional diagnostic testing (115/140, 82.14% vs 50/140, 35.71%, P < 0.05). The percentage of mNGS-positive patients was significantly higher than that of conventional testing-positive patients with regard to bacterial detection (P < 0.01), but no significant differences were found with regard to fungal detection (P = 0.67). Significant statistical differences were found between mixed infection cases (15, 22.70%) and single infection cases (4, 7.84%) in terms of diabetes (P = 0.03). The most frequent pattern of mixed infection was bacteria and fungi mixed infection (40, 40/89 = 44.94%), followed by bacteria mixed infection (29, 29/89 = 32.58%). The sensitivity of mNGS in pulmonary infection diagnosis was much higher than that of conventional test (89.17% vs 50.00%; P < 0.01), but the specificity was the opposite (75.00% vs 81.82%; P > 0.05). CONCLUSION: mNGS is a valuable tool for the detection of pulmonary infections, especially mixed pulmonary infections. The most common combinations we found were bacterial-fungal coinfection and bacterial-bacterial coinfection. Still, there are many challenges in the clinical application of mNGS in the diagnosis of pulmonary infections. There is still a lot of work to be done in interpreting the mNGS reports, because both clinical judgment and literature analysis strategy need to be refined.

A rapid way of formulation development revealing potential synergic effects on numerous antimicrobial combinations against foodborne pathogens.

The interactions between various essential oils (EOs) were evaluated for the development of antimicrobial formulations. A full factorial design was applied for testing eight EOs (Mustard, Thyme, Garlic, Oregano, Chinese cinnamon, Cinnamon bark, Red bergamot, Winter savory) against nine bacteria (E.coli O157:H7 RM1239, E.coli O157:H7 RM 1931, E.coli O157:H7 RM 1933, E.coli O157:H7 RM 1934, E.coli O157:H7 380-94, Listeria monocytogenes LM 1045, Listeria innocua ATCC 51742, Salmonella Typhimurium SL 1344, Salmonella enterica Newport ATCC 6962) and two molds (Penicillium chrysogenum ATCC 10106, Aspergillus niger ATCC 1015). Results showed that combinations of Thyme + Oregano, Oregano + Cinnamon bark, Chinese cinnamon + Cinnamon bark have shown high interactions in Factorial design and validated to be mostly additive effects against tested bacteria. The combination of Mustard + Thyme, Mustard + Garlic, and Thyme + Garlic EOs showed high interactions and also all additive effects against tested molds. The corresponding results of Factorial design and checkerboard render the designation to demonstrate the highly efficient formulations and interactions rapidly among abundant mixtures.

Inelastic hyperspectral Scheimpflug lidar for microalgae classification and quantification.

An inelastic hyperspectral Scheimpflug lidar system was developed for microalgae classification and quantification. The correction for the refraction at the air-glass-water interface was established, making our system suitable for aquatic environments. The fluorescence spectrum of microalgae was extracted by principal component analysis, and seven species of microalgae from different phyla have been classified. It was verified that when the cell density of Phaeocystis globosa was in the range of ${{1}}{{{0}}^4}\sim{{1}}{{{0}}^6}\;{\rm{cell}}\;{\rm{m}}{{\rm{L}}^{- 1}}$, the cell density had a linear relationship with the fluorescence intensity. The experimental results show our system can identify and quantify microalgae, with application prospects for microalgae monitoring in the field environment and early warning of red tides or algal blooms.