Comparison of early and late postoperative outcomes between chordal reconstruction and quadrangular resection in patients with posterior mitral valve prolapse: a single-center retrospective study.

BACKGROUND: To compare the early and late postoperative outcomes of chordal reconstruction (CR) and quadrangular resection (QR) in patients with posterior mitral valve prolapse (PMPL). METHODS: Between January 2008 and December 2018, 305 patients with PMPL who underwent mitral valve plasty (MVP) were included in this retrospective analysis. The CR and QR procedures were performed in 169 patients (CR group) and 136 patients (QR group), respectively. Early and late postoperative outcomes were compared between the groups. RESULTS: Follow-up was complete in 96.4% (294/305) of patients, with a mean follow-up of 81.2 ± 30.4 months. No 30-day mortality was observed in any of the patients. The success rate of the mitral valve repair was similar in both groups (99.4% vs. 98.5%, P = 0.850). The incidence of early postoperative hemolysis was lower in the CR group than in the QR group (0.00% vs. 3.0%, P = 0.024). Postoperative left ventricular end-diastolic diameter (LVEDD) decreased more significantly in the CR group than in the QR group at 3 months (8.15 [1.30,12.65] vs. 3.25 [- 0.05, 8.75] mm, P < 0.001). During follow-up, the overall survival rates were 95.1% and 94.6% in the CR and QR groups, respectively. The incidence of reoperation for moderate or severe mitral regurgitation (MR) was similar in both groups (4.3% vs.5.4%, P = 0.653), but the time interval between the initial operation and reoperation was shorter in the QR group than in the CR group (84.3 ± 36.1 vs. 120.9 ± 27.6 months, P = 0.026). The LVEDD enlargement was more significant in the QR group than in the CR group (4.5 [3.6, 4.5] vs. 2.4 [1.3, 2.8] mm, P < 0.001). CONCLUSION: CR and QR are effective techniques for patients with PMPL. Both techniques resulted in a low incidence of recurrent MR. However, CR can reduce early postoperative hemolysis and LVEDD more significantly. During the long-term follow-up, reoperations due to recurrent MR were performed at a longer interval after the initial operation. LVEDD expansion was better avoided in the CR group.

Advances in Cas12a-Based Amplification-Free Nucleic Acid Detection.

In biomedicine, rapid and sensitive nucleic acid detection technology plays an important role in the early detection of infectious diseases. However, most traditional nucleic acid detection methods require the amplification of nucleic acids, resulting in problems such as long detection time, complex operation, and false-positive results. In recent years, clustered regularly interspaced short palindromic repeats (CRISPR) systems have been widely used in nucleic acid detection, especially the CRISPR-Cas12a system, which can trans cleave single-stranded DNA and can realize the detection of DNA targets. But, amplification of nucleic acids is still required to further improve detection sensitivity, which makes Cas12a-based amplification-free nucleic acid detection methods a great challenge. This article reviews the recent progress of Cas12a-based amplification-free detection methods for nucleic acids. These detection methods apply electrochemical detection methods, fluorescence detection methods, noble metal nanomaterial detection methods, and lateral flow assay. Under various optimization strategies, unamplified nucleic acids have the same sensitivity as amplified nucleic acids. At the same time, the article discusses the advantages and disadvantages of each method and further discusses the current challenges such as off-target effects and the ability to achieve high-throughput detection. Amplification-free nucleic acid detection technology based on CRISPR-Cas12a has great potential in the biomedical field.

A plasma 3-marker microRNA biosignature distinguishes spinal tuberculosis from other spinal destructive diseases and pulmonary tuberculosis.

Accurate spinal tuberculosis (TB) diagnosis is of utmost importance for adequately treating and managing the disease. Given the need for additional diagnostic tools, this study aimed to investigate the utility of host serum miRNA biomarkers for diagnosing and distinguishing spinal tuberculosis (STB) from pulmonary tuberculosis (PTB) and other spinal diseases of different origins (SDD). For a case-controlled investigation, a total of 423 subjects were voluntarily recruited, with 157 cases of STB, 83 cases of SDD, 30 cases of active PTB, and 153 cases of healthy controls (CONT) in 4 clinical centers. To discover the STB-specific miRNA biosignature, a high-throughput miRNA profiling study was performed in the pilot study with 12 cases of STB and 8 cases of CONT using the Exiqon miRNA PCR array platform. A bioinformatics study identified that the 3-plasma miRNA combination (hsa-miR-506-3p, hsa-miR-543, hsa-miR-195-5p) might serve as a candidate biomarker for STB. The subsequent training study developed the diagnostic model using multivariate logistic regression in training data sets, including CONT(n=100) and STB (n=100). Youden's J index determined the optimal classification threshold. Receiver Operating Characteristic (ROC) curve analysis showed that 3-plasma miRNA biomarker signatures have an area under the curve (AUC) = 0.87, sensitivity = 80.5%, and specificity = 80.0%. To explore the possible potential to distinguish spinal TB from PDB and other SDD, the diagnostic model with the same classification threshold was applied to the analysis of the independent validation data set, including CONT(n=45), STB(n=45), brucellosis spondylitis (BS, n=30), PTB (n=30), spinal tumor (ST, n=30) and pyogenic spondylitis (PS, n=23). The results showed diagnostic model based on three miRNA signatures could discriminate the STB from other SDD groups with sensitivity=80%, specificity=96%, Positive Predictive Value (PPV)=84%, Negative Predictive Value (NPV)=94%, the total accuracy rate of 92%. These results indicate that this 3-plasma miRNA biomarker signature could effectively discriminate the STB from other spinal destructive diseases and pulmonary tuberculosis. The present study shows that the diagnostic model based on 3-plasma miRNA biomarker signature (hsa-miR-506-3p, hsa-miR-543, hsa-miR-195-5p) may be used for medical guidance to discriminate the STB from other spinal destructive disease and pulmonary tuberculosis.

Notch1-mediated tumor suppression in cervical cancer with the involvement of SST signaling and its application in enhanced SSTR-targeted therapeutics.

The role of Notch signaling in cervical cancer is seemingly controversial. To confirm the function of Notch signaling in this type of cancer, we established a stable Notch1-activated cervical cancer HeLa cell line. We found that Notch1 activation resulted in apoptosis, cell cycle arrest, and tumor suppression. At the molecular level, we found that a variety of genes associated with cyclic AMP, G protein-coupled receptor, and cancer signaling pathways contributed to Notch1-mediated tumor suppression. We observed that the expression of somatostatin (SST) was dramatically induced by Notch1 signaling activation, which was accompanied by enhanced expression of the cognate SST receptor subtype 1 (SSTR1) and SSTR2. Certain genes, such as tumor protein 63 (TP63, p63), were upregulated, whereas others, such as B-cell lymphoma 2 (BCL-2), Myc, Akt, and STAT3, were downregulated. Subsequently, knockdown of Notch1-induced SST reversed Notch1-induced decrease of BCL-2 and increase of p63, indicating that Notch1-induced tumor suppression may be partly through upregulating SST signaling. Our findings support a possible crosstalk between Notch signaling and SST signaling. Moreover, Notch-induced SSTR activation could enhance SSTR-targeted cancer chemotherapy. Valproic acid (VPA), a histone deacetylase inhibitor, suppressed cell growth and upregulated the expression of Notch1 and SSTR2. A combination therapy with VPA and the SSTR2-targeting cytotoxic conjugate CPT-SST strongly led to greater suppression, as compared to each alone. Our findings thus provide us with a promising clinical opportunity for enhanced cancer therapy using combinations of Notch1-activating agents and SSTR2-targeting agents.

Exendin-4 alleviates ß-Amyloid peptide toxicity via DAF-16 in a Caenorhabditis elegans model of Alzheimer's disease.

Epidemiological analyses indicate that type 2 diabetes mellitus (T2DM) is a risk factor for Alzheimer's disease (AD). They share common pathophysiological mechanisms. Thus, it has been increasingly suggested that several anti-T2DM drugs may have therapeutic potential in AD. Exendin-4, as a glucagon-like peptide-1 (GLP-1) receptor agonist, is an approved drug used to treat T2DM. In this research, the neuroprotective effect of Exendin-4 was investigated for the first time using transgenic Caenorhabditis elegans. Our results demonstrated that Exendin-4 attenuated the amyloid-ß (1-42) (Aß1-42) toxicity via multiple mechanisms, such as depressing its expression on protein and mRNA and reducing Aß (1-42) accumulation. Exendin-4 at 0.5 mg/ml had been shown to extend life by 34.39% in CL4176 and delay the onset of paralysis in CL4176 and CL2006 which were increased by 8.18 and 8.02%, respectively. With the treatment of Exendin-4, the nuclear translocation of DAF-16 in the transgenic nematode TJ356 was enhanced. Superoxide dismutase-3 (SOD-3), as a downstream target gene regulated by DAF-16, was upregulated on mRNA level and activity. The reactive oxygen species (ROS) level was decreased. In contrast, we observed that the ability of Exendin-4 to regulate SOD was decreased in CL4176 worms with the DAF-16 gene silenced. The activity of SOD and the mRNA level of sod-3 were downregulated by 30.45 and 43.13%, respectively. Taken together, Exendin-4 attenuated Aß (1-42) toxicity in the C. elegans model of AD via decreasing the expression and the accumulation of Aß (1-42). Exendin-4 exhibited the ability of antioxidant stress through DAF-16. With continuous research, Exendin-4 would become a potential therapeutic strategy for treating AD.

A review of spectroscopic probes constructed from aptamer-binding gold/silver nanoparticles or their dimers in environmental pollutants' detection.

The issue of environmental pollutant residues has gained wide public attention all along. Therefore, it is necessary to develop simple, rapid, economical, portable, and sensitive detection techniques, which have become the focus of research in the pollutants detection field. Spectroscopy is one of the most convenient, simple, rapid, and intuitive analytical tools that can provide accurate information, such as ultraviolet spectroscopy, fluorescence spectroscopy, Raman spectroscopy, plasmon resonance spectroscopy, etc. Gold nanoparticles, silver nanoparticles, and their dimers with unique optical properties are commonly used in the construction of spectroscopic probes. As a class of oligonucleotides that can recognize specific target molecules, aptamers also have a strong ability to recognize small-molecule pollutants. The application of aptamer-binding metal nanoparticles in biosensing detection presents significant advantages for instance high sensitivity, good selectivity, and rapid analysis. And many spectroscopic probes constructed by aptamer-binding gold nanoparticles, silver nanoparticles, or their dimers have been successfully demonstrated for detecting pollutants. This review summarizes the progress, advantages, and disadvantages of aptamer sensing techniques constructed by visual colorimetric, fluorescence, Raman, and plasmon resonance spectroscopic probes combining gold/silver nanoparticles or their dimers in the field of pollutants detection, and discusses the prospects and challenges for their future.

Clinical efficacy and safety of ultra-short-course chemotherapy in treatment of spinal tuberculosis after complete debridement: an observational study.

OBJECTIVE: To evaluate the clinical efficacy and safety of ultra-short-course chemotherapy (<4 months) in treating spinal tuberculosis following complete debridement. METHODS: Clinical data of patients diagnosed with spinal tuberculosis, who underwent surgery with postoperative chemotherapy for < 4 months at the General Hospital of Ningxia Medical University between January 2005 and March 2015, were retrospectively analysed. Clinical manifestations, American Spinal Injury Association grades, states of bone fusion and lesion healing, deformity correction, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) levels and adverse drug reactions, observed before and after surgery and at the final follow-up, were assessed. RESULTS: Sixty patients were included, comprising 26 male and 34 female patients aged 16-78 years (mean, 40.85 years). Patients received postoperative chemotherapy for 3-4 months (mean, 3.61 months) and were followed for 25-129 months (mean, 70.61 months). Spinal tuberculosis recurred after surgery in one patient, who was cured by subsequent surgery. At the final follow-up, no symptoms of tuberculosis, local pain, abscess or sinus were observed. Daily life and working abilities were almost recovered in all patients. ESR and CRP levels were restored to normal, bone grafts fused, lesions healed and neurological functions were recovered. Postoperative chemotherapy-induced complications occurred in 10 patients (16.67%). CONCLUSIONS: Complete debridement plus ultra-short-course chemotherapy for 3-4 months may be safe and efficacious in treating spinal tuberculosis, and requires further investigation.

Banana Peel-Derived Dendrite-Shaped Au Nanomaterials with Dual Inhibition Toward Tumor Growth and Migration.

PURPOSE: In order to prepare functional Au nanoparticles with low toxicity and high antitumor properties, we have used fruit waste (banana peel) to synthesize a new dendrite-shaped gold nanoparticle and used it for the treatment of tumors. METHODS: Dendrite-shaped gold nanoparticle (Au-dendrite) was synthesized through a facile hydrothermal process. The banana peel was used as both the reducing agent and the protective agent for reducing chloroauric acid to obtain Au-dendrite. The safety assessment of the Au-dendrite was conducted by H&E staining of the mouse's eyelid skin and CCK-8 assay. The antitumor effects were evaluated through in vitro tumor cytotoxicity experiments and in vivo treatment of animal tumors. RESULTS: In this work, a new type of gold nanomaterial (Au-dendrite) was synthesized by using a common agricultural waste (banana peel) through a facile hydrothermal process without any extra chemical reducing agent or protective agent. Subsequent experiments showed that, compared with some classical Au nanomaterials, the as-synthesized gold nanocomposites have superior biocompatibility and impressive characteristics of dual inhibition toward tumor growth and migration. CONCLUSION: We successfully synthesized a dendrite-shaped gold nanocomposite which was derived from a common agricultural waste (banana peel). A facile and environmentally friendly synthetic process was proposed accordingly without regular chemical additives. The as-prepared Au-dendrite nanocomposites not only had better biocompatibility than some classical gold nanoparticles but also exhibited unique advantages in tumor inhibition.

Porous ZnO modified silk sutures with dual light defined antibacterial, healing promotion and controlled self-degradation capabilities.

Current sutures have disadvantages such as poor antibacterial activities, low healing effects, and a lack of self-degradation ability. To solve these problems, here a biocompatible and dual light (yellow and NIR light) responsive porous ZnO (PZ) was synthesized to modify silk thread to improve the healing rate, antibacterial activities and controlled self-degradation speed simultaneously. The prepared silk thread was characterized by using scanning electron microscopy (SEM) and X-ray diffractometry (XRD). Besides, the antibacterial activity, degradation, dual light responsive capability and cytocompatibility of the sample were evaluated. The obtained data strongly encourage the application of this silk thread for wound treatment. Furthermore, in vivo evaluation in mice revealed that the silk thread reduced surgical-site infection and enhanced wound healing. Therefore, this silk thread shows potential for application in wound treatment clinically.

NaCl: for the safer in vivo use of antibacterial silver based nanoparticles.

BACKGROUND: As antibiotics progressively cease to be effective, silver based nanoparticles (SBNs), with broad antibacterial spectrum, might be the last line of defense against malicious bacteria. Unfortunately, there are still no proper SBNs-based strategies for in vivo antibacterial therapies. In this article, new carbon membrane packaged Ag nanoparticles (Ag-C) were synthesized. We assessed the effect of Ag-C with NaCl on size, cytotoxicity, antibacterial properties, metabolism and sepsis models. METHODS: The size of Ag-C with NaCl was accessed with UV-vis, TEM and SEM. Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa were used to illustrate the antibacterial properties of SBNs affected by NaCl. L929 and 3T3 cell lines were cultured in vitro; CCK-8 assay was used to test cytotoxicity. Then, we explored the metabolism of Ag-C with NaCl in vivo. Finally, the effect of Ag-C with 4× NaCl on sepsis was observed. RESULTS: NaCl could regulate the size of Ag-C. Ag-C exhibited superior antibacterial properties compared to similar sized pure Ag nanoparticles. Furthermore, the addition of NaCl could not only reduce the cytotoxicity of Ag-C, but could also continue to discharge Ag-C from major organs. Based on these factors, this method was used to treat a sepsis model (induced via cecal ligation and puncture), and it achieved satisfactory survival results. CONCLUSION: This discovery, though still in its infancy, could significantly improve the safety and feasibility of SBNs and could potentially play an important role in modern in vivo antibacterial applications. Thus, a new method to combating the growing threat from drug-resistant bacteria could be possible. NaCl is the key to excretion of SBNs after in vivo antibacterial use.

3D printed self-driven thumb-sized motors for in-situ underwater pollutant remediation.

Green fuel-driven thumb sized motors (TSM) were designed and optimized by 3D printing to explore their in-situ remediation applications in rare studied underwater area. Combined with areogel processing and specialized bacteria domestication, each tiny TSM could realize large area pollutant treatment precisely in an impressive half-automatically manner.

A highly efficient, low-toxic, wide-spectrum antibacterial coating designed for 3D printed implants with tailorable release properties.

Herein, a highly customized and broad-spectrum antibacterial implant was prepared through the combination of 3D printing technology and surface nano-modification. The antibacterial coating, which consists of the film-forming agent polyvinyl alcohol (PVA), polyethylene acid (PAA), and green-synthesized silver nanoparticles (Ag-NPs), was modified on the surface of a 3D-printed implant. The small-sized Ag-NPs (<10 nm) showed potent broad spectrum activity and good biocompatibility in relatively low concentration. Moreover, through changing the content of the Ag-NPs and the proportion of PVA and PAA, the loadings and release rate of Ag-NPs could be controlled according to actual requirements, achieving the goal of precise treatment. Animal experiments demonstrated that the implant system exhibited superior anti-infection performance, which could effectively reduce the postoperative infection risk of implant materials, consequently promoting the practical process of 3D printed implants.

Risk of gastrointestinal complications in breast cancer patients treated with neratinib: a meta-analysis.

BACKGROUNDS: Neratinib is a potent EGFR/HER2 kinase inhibitor. Gastrointestinal complications (i.e. diarrhea, vomiting and nausea) are the most common adverse events. In this study, we aimed to investigate (1) the overall incidence and relative risk (RR) of diarrhea, vomiting and nausea and (2) whether combination neratinib therapy increased the incidence of gastrointestinal complications versus neratinib alone. METHODS: Relevant studies were identified from the PubMed database, from abstracts presented at the American Society of Clinical Oncology annual conference and from the Web of Science database. Incidences, RRs, and 95% confidence intervals (CIs) were calculated. RESULTS: The incidences of all-grade diarrhea, vomiting and nausea in the neratinib groups were 89% (95% CI = 77-95%), 31% (95% CI = 25-37%) and 44% (95% CI = 33-55%), respectively. The neratinib arms significantly increased the risk of diarrhea and vomiting in comparison with the control groups (diarrhea: all-grade, RR = 2.06, 95% CI = 1.38-3.08, P = 0.0004; grade 3/4, RR = 8.77, 95% CI = 2.91-26.40, P = 0.0001; vomiting: all-grade, RR = 2.02, 95% CI = 1.10-3.71, P = 0.02; grade 3/4, RR = 7.10, 95% CI = 3.33-15.15, P < 0.00001). CONCLUSIONS: Our meta-analysis demonstrates that the neratinib arms are associated with a significantly increased risk of diarrhea and vomiting.

Full Spectrum Visible LED Light Activated Antibacterial System Realized by Optimized Cu2O Crystals.

Assisted by three-dimensional printing technology, we proposed and demonstrated a full spectrum visible light activated antibacterial system by using a combination of 500 nm sized Cu2O crystals and light-emitting diode (LED) lamps. Further improved antibacterial ratios were achieved, for the first time, with pure Cu2O for both Gram-positive bacteria and Gram-negative bacteria among all of the six different color LED lamps. For practical antibacterial applications, we revealed that the nonwoven fabric could act as excellent carrier for Cu2O crystals and provide impressive antibacterial performance. Furthermore, integrated with our self-developed app, the poly(ethylene terephthalate) film loaded with Cu2O crystals also showed significant antibacterial property, thus making it possible to be applied in field of touch screen. The present research not only provided a healthier alternative to traditional ultraviolet-based sterilization but also opened an auto-response manner to decrease the rate of microbial contamination on billions of touch screen devices.

The first visually observable three-mode antibiotic switch and its relative 3D printing assisted applications.

The first visible three-mode switchable antibiotic nanocomposite, including "Packaged" (low toxicity and high stability), "On" (potent antibacterial activity, including drug-resistant strains) and "Off" (easy separation) modes, was synthesized to address several problems caused by antibiotic abuses. Some potential applications were discussed by using animal experiments and 3D printing separately.