The impact of the 2019 ESC/EAS dyslipidaemia guidelines on real-world initial lipid-lowering therapy in patients with acute myocardial infarction.

This study aimed to investigate the impact of the latest guidelines on the real-world clinical practice of initial lipid-lowering therapy, especially on the use of ezetimibe and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors in China. All adult patients diagnosed with acute myocardial infarction in our hospital between August 31, 2018, and August 31, 2020, were divided into the following 2 groups: those patients treated before the latest guideline release, and those patients treated after the release. A propensity score-matched method was used, and logistic regression was used to assess the association with intensive statin, ezetimibe and PCSK9 inhibitor usage together with treatment results between the 2 groups. A total of 325 patients were enrolled in this study, including 141 patients who were admitted before the release of the latest guideline and 184 patients who were admitted after the release. After a median follow-up time of 8.20 months, the mean low-density lipoprotein cholesterol was 1.87 ±â€…0.59 mmol/L (1.87 ±â€…0.55 in the before group vs 1.88 ±â€…0.62 in the after group, P = .829). After propensity score matching, the initial usage of intensive statin therapy was decreased after guideline release without statistical significance (17.00% vs 28.00%, P = .090), whereas the usage of ezetimibe and PCSK9 inhibitors was increased (19.00% vs 8.00%, P = .039; and 10.00% vs 3.00%, P = .085, respectively). In logistic regression models, the release of the guideline was associated with a statistically significantly increased use of ezetimibe (odds ratio [OR]: 1.91; 95% confidence interval [CI]: 1.21, 3.02; P = .005), a marginally decreased use of intensive statins (OR: 0.68; 95% CI: 0.45, 1.03; P = .069) and a marginally increased use of PCSK9 inhibitors (OR: 1.31; 95% CI: 0.98, 1.76; P = .068). In this single-center, real-world data analysis, after the release of the 2019 European Society of Cardiology/European Atherosclerosis Society guidelines, an increasing number of patients with a recent acute myocardial infarction were initially receiving ezetimibe and PCSK9 inhibitors.

Treponema pallidum recombinant protein Tp47 enhanced interleukin-6 secretion in human dermal fibroblasts through the toll-like receptor 2 via the p38, PI3K/Akt, and NF-κB signalling pathways.

Interleukin-6 (IL-6) is a multi-effective cytokine involved in multiple immune responses. Whether fibroblasts also turn out to be a cytokine IL-6 factory during interaction with Treponema pallidum is not yet understood. To explore whether fibroblasts participate in inflammation due to syphilis, a series of experiments were performed to explore the role of T. pallidum lipoprotein Tp47 in IL-6 production in human dermal fibroblasts. The Toll-like receptor 2 (TLR2) and participating signalling pathways in this process were also evaluated. The results showed that the expressions of IL-6 and the protein levels of TLR2 in fibroblasts were upregulated after stimulation with Tp47, and this effect was impeded by the TLR2 inhibitor C29. In addition, Tp47 promoted the phosphorylation of p38, PI3K/Akt, and nuclear factor-kappaB (NF-κB), and the translocation of NF-κB in fibroblasts. Moreover, p38, PI3K, and NF-κB inhibitors significantly reduced IL-6 production in fibroblasts stimulated with Tp47. Furthermore, the TLR2 inhibitor C29 inhibited the phosphorylation of p38, Akt, and NF-κB, and the translocation of NF-κB in fibroblasts. In conclusion, our results showed that Tp47 enhanced IL-6 secretion in human dermal fibroblasts through TLR2 via p38, PI3K/Akt, and NF-κB signalling pathways. These findings contribute to our understanding of syphilis inflammation.

Clinical efficacy of selenium supplementation in patients with Hashimoto thyroiditis: A systematic review and meta-analysis.

BACKGROUND: Evidence suggests that selenium supplementation could be useful in the treatment of Hashimoto thyroiditis (HT), but the available trials are heterogeneous. This study investigates clinically relevant effects of selenium supplementation in patients with HT. METHODS: A systematic search was performed in PubMed, Web of Science, EMBASE, Scopus, and the Cochrane Library. The latest update was performed on December 3, 2022. We investigated the changes in thyroid peroxidase antibodies (TPOAb) and thyroglobulin antibodies (TgAb) after selenium supplementation. The effect sizes were expressed as weighted mean difference (WMD) with 95% confidence intervals (CIs). RESULTS: After screening and full-text assessment, 7 controlled trials comprising 342 patients were included in the systematic review. The results showed that there was no significant change in TPOAb levels (WMD = -124.28 [95% CI: -631.08 to 382.52], P = .631, I2 = 94.5%) after 3 months of treatment. But there was a significant decrease in TPOAb levels (WMD = -284.00 [95% CI: -553.41 to -14.60], P < .05, I2 = 93.9%) and TgAb levels (WMD = -159.86 [95% CI: -293.48 to -26.24], P < .05, I2 = 85.3%) after 6 months of treatment. CONCLUSIONS: Selenium supplementation reduces serum TPOAb and TgAb levels after 6 months of treatment in patients with HT, but future studies are warranted to evaluate health-related quality or disease progression.

False-Positive Results of SARS-CoV-2 RT-PCR in Oropharyngeal Swabs From Vaccinators.

Real-time reverse transcription-polymerase chain reaction (RT-PCR) is the gold standard for diagnosing coronavirus disease 2019 (COVID-19). However, RT-PCR may yield false-positive results, leading to unnecessary countermeasures. Here, we report a "positive" nucleic acid test on a 10-pooled sample during the routine screening that caused many adverse societal effects, and financial and resource losses. However, they were subsequently determined to be a case of vaccine contamination. This case study increases awareness of false-positive RT-PCR results for SARS-CoV-2, especially when participants are vaccinators. Moreover, it could provide relevant suggestions to prevent the recurrence of such incidents.

The Role of Second Generation Sequencing Technology and Nanomedicine in the Monitoring and Treatment of Lower Extremity Deep Vein Thrombosis Susceptibility Genes.

To study effect of nanomedicine on lower extremity deep vein thrombosis (LEDVT) and its correlation with susceptibility genes (SGs), preliminary nanoparticle LSA was constructed using lauric acid and stearic acid, and CTAB-HAuCL4-TEOS (CHT) was obtained using cetyltrimethyl ammonium bromide (CTAB), chloroauric acid (HAuCL4), and tetraethoxysilane (TEOS) to prepare UK-LSA-CHT by combining with urokinase (UK). 20 rabbits were grouped into UK-LSA-CHT, LSA, UK, and D0 group. Human umbilical vein endothelial cells (HUVEC) were selected for cytotoxicity test. The plasma endothelin (ET-1), interleukin 6 (IL-6), and nuclear factor κß (NF-κß) of the rabbits were detected with double antibody sandwich method. Expression of platelet activating factor (PAF) was detected by immumohistochemical staining. Genotype distribution was detected with the second-generation sequencing technology (SGST). The results showed that expressions of ET-1, IL-6, and NF-κß) in UK-LSA-CHT group were lower than those in the LSA group and the UK group after 12 hours (P < 0.05). Frequency of allele G and T, and GT and TT genotype ratio of SG NOS3 rs1799983 in UK -LSA-CHT group were less than those in LSA and UK group (P < 0.05). UK-LSA-CHT group had observably lower value in PAF positive expression than LSA and UK groups (P < 0.05). In short, UK-LSA-CHT had good biocompatibility and safety and good therapeutic effect on LEDVT. N0S3 rs1799983 alleles G and T may be the key risk factors for the occurrence and development of LEDVT.

Cancer Therapy Based on Smart Drug Delivery with Advanced Nanoparticles.

BACKGROUND: Cancer, as one of the most dangerous disease, causes millions of deaths every year. The main reason is the absence of an effective and thorough treatment. Drug delivery systems have significantly reduced the side-effect of chemotherapy. Combined with nanotechnology, smart drug delivery systems including many different nanoparticles can reduce the side-effect of chemotherapy better than traditional drug delivery systems. METHODS: In this article, we will describe in detail the different kinds of nanoparticles and their mechanisms emphasizing the triggering factors in drug delivery. Besides, the application of smart drug delivery systems in imaging will be introduced. RESULTS: Combined with nanotechnology, smart drug delivery systems including many different nanoparticles can reduce the side-effect of chemotherapy better than traditional drug delivery systems. CONCLUSION: Despite considerable progress in nanoparticle research over the past decade, such as smart drug delivery systems for the treatment of cancer, molecular imaging probes and the like. The range of nanoparticles used in multifunction systems for imaging and drug delivery continues to grow and we expect this dilatation to continue. But to make nanoparticles truly a series of clinical products to complement and replace current tools, constant exploration efforts and time are required. Overall, the future looks really bright.

Applications of Nanoparticles Probes for Prostate Cancer Imaging and Therapy.

Prostate cancer (PCa) is the most common type of cancer in men with high morbidity and mortality. However, the current treatment with drugs often leads to chemotherapy resistance. It is known that the multi-disciplines research on molecular imaging is very helpful for early diagnosing, staging, restaging and precise treatment of PCa. In the past decades, the tumor-specific targeted drugs were developed for the clinic to treat prostate cancer. Among them, the emerging nanotechnology has brought about many exciting novel diagnosis and treatments systems for PCa. Nanotechnology can greatly enhance the treatment activity of PCa and provide novel theranostics platform by utilizing the unique physical/chemical properties, targeting strategy, or by loading with imaging/therapeutic agents. Herein, this chapter focuses on state-of-art advances in imaging and diagnosing PCa with nanomaterials and highlights the approaches used for functionalization of the targeted biomolecules, and in the treatment for various aspects of PCa with multifunctional nanoparticles, nanoplatforms and nanodelivery system.

pH/redox responsive core cross-linked nanoparticles from thiolated carboxymethyl chitosan for in vitro release study of methotrexate.

A novel amphiphilic thiolated carboxymethyl chitosan was synthesized. It self-assembled into disulfide bond cross-linked nanoparticles in deionized water. The TEM showed that these nanoparticles had a core-shell structure with an average diameter of 160 nm. Dynamic light scattering showed that the nanoparticles were stable in water solution. The particle size changed with pH values and GSH concentrations, and reached a maximum diameter at pH 7.0 and 20mM GSH respectively, exhibiting an obvious pH/redox responsibility. Methotrexate was encapsulated in nanoparticles reaching encapsulation efficiency as much as 43.4%. Release profiles of methotrexate showed a release rate of 19 wt% in pH 7.4 buffer containing 10 µM GSH, whereas as high as 93 wt% in pH 5.0 buffer containing 20mM GSH, indicating that the nanoparticles may be used for tumor-specific drug release. The anticancer activity test in vitro showed that the inhibition rate of methotrexate-loaded nanoparticles against HeLa cells reached 90%.