Microplastics are associated with elevated atherosclerotic risk and increased vascular complexity in acute coronary syndrome patients.

BACKGROUND: Microplastics, widely present in the environment, are implicated in disease pathogenesis through oxidative stress and immune modulation. Prevailing research, primarily based on animal and cell studies, falls short in elucidating microplastics' impact on human cardiovascular health. This cross-sectional study detected blood microplastic concentrations in patients presenting with chest pain using pyrolysis-gas chromatography/mass spectrometry and evaluating inflammatory and immune markers through flow cytometry, to explore the potential effects of microplastic on acute coronary syndrome. RESULTS: The study included 101 participants, comprising 19 controls and 82 acute coronary syndrome cases. Notably, acute coronary syndrome patients exhibited elevated microplastic concentrations, with those suffering from acute myocardial infarction presenting higher loads compared to those with unstable angina. Furthermore, patients at intermediate to high risk of coronary artery disease displayed significantly higher microplastic accumulations than their low-risk counterparts. A significant relationship was observed between increased microplastic levels and enhanced IL-6 and IL-12p70 contents, alongside elevated B lymphocyte and natural killer cell counts. CONCLUSION: These results suggest an association between microplastics and both vascular pathology complexity and immunoinflammatory response in acute coronary syndrome, underscoring the critical need for targeted research to delineate the mechanisms of this association. HIGHLIGHTS: 1 Blood microplastic levels escalate from angiographic patency, to angina patients, peaking in myocardial infarction patients. 2 Microplastics in acute coronary syndrome patients are predominantly PE, followed by PVC, PS, and PP. 3 Microplastics may induce immune cell-associated inflammatory responses in acute coronary syndrome patients.

Families' perception of terminal patients' prognosis awareness is associated with families' own grief: Evidence from a hospital in China.

AIM: The aim of the study was to explore how families' perceptions of dying patients' prognosis awareness influence families' grief. DESIGN: A cross-sectional design was adopted. METHOD: Data were collected from a survey of family caregivers of deceased patients through a tertiary hospital in Mainland China between October 2018 and April 2021. One question asked about families' perceptions of patients' awareness of their prognosis, and the Chinese Grief Reaction Assessment Form was used to measure grief. A multiple linear regression with control variables was run to test the link. Missing data were handled with multiple imputation. RESULTS: A total of 181 participants were involved in the analyses. After whether the patient received professional end-of-life care in the last days, the place of death and several basic information variables were controlled, families' grief was more intense when they were sure that patients were unaware of the terminal prognosis compared to when they believed that patients were aware or not sure about the patient's awareness. The latter two groups did not differ significantly in grief intensity. CONCLUSION: For Chinese family caregivers in the present study, terminal patients' awareness of their prognosis is more beneficial than harmful to their bereavement adaptation. This raises empirical concerns over the assumption that truth is harmful and the nondisclosure pattern on such a basis. IMPACT: The findings extend knowledge on the outcomes of information disclosure from the perspective of bereaved family caregivers. Meanwhile, it informs services for the dying and the bereaved: When making decisions about prognosis disclosure to terminally ill patients, potential impacts on not only patients but also families need to be fully considered. For families who are sure that the patient was never aware of the prognosis, additional support ought to be provided to address their intense grief reactions. PATIENT OR PUBLIC CONTRIBUTION: Several professional caregivers helped revise the questionnaire.

Glomerular diseases after immune checkpoint inhibitors use: What do We know so far?

The research and application of immune checkpoint inhibitors (ICIs) have enormously promoted the progression of tumor treatment. Gradual implementation of ICIs in clinical practice is largely limited as they exert uncontrolled collateral effects on the immune system, such as immune-related adverse events (irAEs); this includes rarely reported glomerular diseases. This study aimed to describe the clinical and pathological manifestation of ICIs-induced glomerular diseases and focused on the mechanism and therapeutic strategy for glomerular diseases associated with ICIs. The data of 53 patients with glomerular diseases related to ICIs were retrieved from the PubMed database. The most frequently reported ICIs-related glomerular diseases were pauci-immune glomerulonephritis (28.3%), podocytopathies (26.4%), and immune-complex glomerulonephritis (18.9%). Moreover, anti-PD1 antibodies were the most commonly used ICIs (71.4%). Most patients receiving ICIs discontinued the treatment (89.4%) and were initiated with steroids (87.2%). Rituximab was also useful in the treatment, especially for renal vasculitis. Rechallenging ICIs could be considered for cancer progression or as salvage therapy, where rechallenging ICI therapy with steroids may be beneficial. We believe the treatment should be personalized based on the degree of renal pathology, serum creatinine (Scr), and tumor progression to obtain a good prognosis.

Family caregivers' perceptions about patients' dying and death quality influence their grief intensity.

AIMS AND OBJECTIVES: To understand the influence of family caregivers' perceptions about patients' dying and death quality on their grief intensity. BACKGROUND: Dying patients and their family caregivers face life-limiting illness together, and they work jointly to negotiate shared understandings and mutual adaptation to losses. DESIGN: Cross-sectional data were collected via an online survey. The manuscript followed the STROBE report guideline. METHODS: Family caregivers of patients who had died within 8-365 days prior were recruited. The Quality of Dying and Death Questionnaire (QDDQ) (translated into Mandarin) and the Chinese Grief Reaction Assessment Form (GRAF) were used to measure the two key variables. Multivariate linear regression was performed to explore the links between the two variables while controlling for potential confounders. RESULTS: Data were collected from 170 bereaved Chinese caregivers, and 150 cases were involved in the analysis. The four-factor structure of the QDDQ was appropriate for Chinese participants. After controlling whether end-of-life care was provided and families' satisfaction with physicians' and nurses' services, regressions revealed that more intense grief of the bereaved caregivers was associated with better symptom control for and worse transcendence of the deceased patient. Moreover, those who believed that the deceased had fulfilled his or her family duties before death experienced less intense grief, and the participant's relationship with the deceased also made a difference. CONCLUSION: Two aspects of patients' dying and death quality perceived by family caregivers, namely symptom control and transcendence, have opposite influences on caregivers' grief intensity.

Reduced anogenital distance, hematuria and left renal hypoplasia in a patient with 13q33.1-34 deletion: case report and literature review.

BACKGROUND: 13q33-q34 microdeletions are rare chromosomal aberrations associated with a high risk of developmental disability, facial dysmorphism, cardiac defects and other malformation of organs. It is necessary to collect and report evidence of this rare chromosome mutation to improve the prognosis of this rare disease. CASE PRESENTATION: We report a patient harboring an 11.56 Mb microdeletion at 13q33.1-34 region, which contains about 30 OMIM genes. Besides the common clinical manifestations such as facial dysmorphism, developmental delay, intellectual disability, epilepsy, and congenital heart disease, she also suffered from a reduced anogenital distance, hematuria and left renal hypoplasia. Most related cases were characterized by facial deformity and heart defects, but there were few reports on renal malformation, especially regarding renal hypoplasia with hematuria. CONCLUSION: We have reported a patient suffering from a reduced anogenital distance, hematuria and left renal hypoplasia. A de novo 11.56 Mb deletion ranging from 13q33.1 to 13q34 (Chr13:103542220-115,106,996) was found by SNP-array analysis. It might be the first time for hematuria and renal hypoplasia to be reported as symptoms of 13q33-q34 deletion syndrome Neurodevelopmental disability, heart defects and urogenital/anorectal anomalies may be resulted from common or overlapping regions of deletion in chromosome bands 13q33.1-q34 and may share a common molecular mechanism.

Dysregulation of calcium channels decreases parasecretion in pancreatic ß-cells in rats born small for gestational age.

OBJECTIVE: To investigate the role of intrauterine malnourishment in the development and function of pancreatic islet ß-cells. METHODS: Whole-cell patch clamping was used to record voltage-gated calcium channel (VGCC)-mediated currents. Insulin secretion was detected by measuring capacitance using a sequence of sine wave stimuli. VGCC currents and insulin secretion were measured in the small for gestational age (SGA) group treated with human recombinant growth hormone (hGH). RESULTS: The membrane capacitance in the SGA group (6.4 ± 0.9 fF/Pf) was significantly reduced. Calcium current density and peak current density in the SGA group were also markedly decreased, whereas other measurements of calcium channels were unaltered. Treatment with hGH significantly rescued the membrane capacitance, whereas calcium channels were not affected. CONCLUSION: Our data suggest that decreased ß-cell secretion is caused by a decreased expression of calcium channels and reduced calcium currents. hGH restores ß-cell secretion in SGA animals, possibly independently of VGCC.

Synthesis and Characterization of Curcumin-Functionalized HP-ß-CD-Modified GoldMag Nanoparticles as Drug Delivery Agents.

Curcumin, a polyphenol extracted from turmeric (Curcuma longa), has emerged as a potent multimodal cancer-preventing agent. It may attenuate the spread of cancer and render chemotherapy more effective. However, curcumin is neither well absorbed nor well retained in the blood, resulting in low efficacy. In an attempt to enhance the potency and to improve the bioavailability of curcumin, new delivery agents, hydroxypropyl-beta-cyclodextrin (HP-ß-CD)-modified GoldMag nanoparticles (CD-GMNs) were designed and synthesized to incorporate curcumin. The CD-GMNs were characterized by Fourier Transform Infrared Spectroscopy (FT-IR), Thermo-gravimetric Analysis (TGA), X-ray Diffraction (XRD), Dynamic Light Scattering measurements (DLS), Transmission Electron Microscopy (TEM) and Vibrating Sample Magnetometer (VSM) analyses. For the magnetic carrier of CD-GMNs, the content of HP-ß-CD was 26.9 wt%. CD-GMNs have a saturation magnetization of 22.7 emu/g with an average hydrodynamic diameter of 80 nm. The curcumin loading, encapsulation efficiency and releasing properties in vitro were also investigated. The results showed that the drug encapsulation ratio was 88% and the maximum curcumin loading capacity of CD-GMNs was 660 µg/5 mg. In vitro drug release studies showed a controlled and pH-sensitive curcumin release over a period of one week. Collectively, our data suggest that HP-ß-CD-modified GoldMag nanoparticles can be considered to form a promising delivery system for curcumin to tumor sites. Targeting can be achieved by the combined effects of the application of an external magnetic field and the effect on drug release of lower pH values often found in the tumor microenvironment.

RBAP, a rhodamine B-based derivative: synthesis, crystal structure analysis, molecular simulation, and its application as a selective fluorescent chemical sensor for Sn2+.

A new fluorescent chemosensor based on a Rhodamine B and a benzyl 3-aminopropanoate conjugate (RBAP) was designed, synthesized, and structurally characterized. Its single crystal structure was obtained and analyzed by X-ray analysis. In a MeOH/H2O (2:3, v/v, pH 5.95) solution RBAP exhibits a high selectivity and excellent sensitivity for Sn2+ ions in the presence of many other metal cations. The binding analysis using the Job's plot suggested the RBAP formed a 1:1 complex with Sn2+.

A bibliometric analysis of the knowledge related to mental health during and post COVID-19 pandemic.

Objective: COVID-19 led to a horrific global pandemic, with strict lockdowns and prolonged indoor stays increasing the risk of mental health problems, affecting people of different ages, genders, regions, and types of work to varying degrees. This study provides a bibliometric summary of the knowledge map related to mental health during and post COVID-19 pandemic. Methods: Publications related to mental health during and post COVID-19 pandemic were searched in the Web of Science Core Collection (WoSCC) database through March 19, 2024. After screening the search results, the literature included in the final was first quantitatively analyzed using GraphPad Prism software and then visualized using VOSviewer, CiteSpace, and R (the bibliometrix package). Results: The 7,047 publications from 110 countries were included, with the highest number of publications from China and the United States, and the number of publications related to mental health during and post the COVID-19 pandemic increased annually until 2023, after which it began to decline. The major institutions were University of Toronto, University of London, Harvard University, King's College London, University College London, University of California System, University of Melbourne, Institut National De La Sante Et De La Recherche Medicale (Inserm), Mcgill University, and University of Ottawa; Frontiers in Psychiatry had the highest number of publications, and the Journal of Affective Disorders had the highest number of co-citations; 36,486 authors included, with Xiang, Yu-Tao, Cheung, Teris, Chung, Seockhoon published the most papers, and World Health Organization, Kroenke K, and Wang CY were the most co-cited; epidemiologically relevant studies on mental health related to COVID-19, and the importance of mental health during normalized epidemic prevention and control are the main directions of this research area, especially focusing on children's mental health; "pandemic," "sars-cov-2," "epidemic," "depression," "coronavirus anxiety," "anxiety," "longitudinal," "child," "coronavirus anxiety," "longitudinal," "child," and "coronavirus" are the top keywords in recent years. Conclusion: This comprehensive bibliometric study summarizes research trends and advances in mental health during and after the COVID-19 Pandemic. It serves as a reference for mental health research scholars during and after the COVID-19 pandemic, clarifying recent research preoccupations and topical directions.

Maternal exposure to E 551 during pregnancy leads to genome-wide DNA methylation changes and metabolic disorders in the livers of pregnant mice and their fetuses.

The widespread use of nanoparticles in the food industry has raised concerns regarding their potential adverse effects on human health, particularly in vulnerable populations, including pregnant mothers and fetuses. However, studies evaluating the reproductive and developmental toxicity of food-grade nanomaterials are limited. This study investigated the potential risks of prenatal dietary exposure to food-grade silica nanoparticles (E 551) on maternal health and fetal growth using conventional toxicological and epigenetic methods. The results showed that prenatal exposure to a high-dose of E 551 induces fetal resorption. Moreover, E 551 significantly accumulates in maternal and fetal livers, triggering a hepatic inflammatory response. At the epigenetic level, global DNA methylation is markedly altered in the maternal and fetal livers. Genome-wide DNA methylation sequencing revealed affected mCG, mCHG, and mCHH methylation landscapes. Subsequent bioinformatic analysis of the differentially methylated genes suggests that E 551 poses a risk of inducing metabolic disorders in maternal and fetal livers. This is further evidenced by impaired glucose tolerance in pregnant mice and altered expression of key metabolism-related genes and proteins in maternal and fetal livers. Collectively, the results of this study highlighted the importance of epigenetics in characterizing the potential toxicity of maternal exposure to food-grade nanomaterials during pregnancy.

Exosomal GDNF from Bone Marrow Mesenchymal Stem Cells Moderates Neuropathic Pain in a Rat Model of Chronic Constriction Injury.

Both of exosomes derived from mesenchymal stem cells (MSCs) and glial cell line-derived neurotrophic factor (GDNF) show potential for the treatment of neuropathic pain. Here, the analgesic effects of exosomes derived from bone marrow MSCs (BMSCs) were investigated. BMSCs-derived exosomes were isolated and characterized. Chronic constriction injury (CCI) was constructed to induce neuropathic pain in rats, which were then treated with exosomes. Pain behaviors were evaluated by measuring paw withdrawal thresholds and latency. The changes of key proteins, including cytokines, were explored using Western blot and ELISA. Administration of BMSCs-derived exosomes alleviated neuropathic pain, as demonstrated by the decrease of thermal hyperalgesia and mechanical allodynia, as well as the reduced secretion of pro-inflammatory cytokines in CCI rats. These effects were comparable to the treatment of GDNF alone. Mechanically, the exosomes suppressed the CCI-induced activation of TLR2/MyD88/NF-κB signaling pathway, while GDNF knockdown impaired their analgesic effects on CCI rat. BMSCs-derived exosomes may alleviate CCI-induced neuropathic pain and inflammation in rats by transporting GDNF.

Serum cytokine profiles in children with IgA vasculitis with nephritis.

This study aimed to discover novel serum biomarkers for IgA vasculitis with nephritis (IgAVN). The serum of IgA vasculitis (IgAV) patients without nephritis and IgAVN patients not treated with glucocorticoids was analyzed for 440 proteins using a novel quantitative planar protein microarray. To verify the biomarkers, semiquantitative immunofluorescence analysis was performed on selected differential cytokines in a separate cohort of kidney tissue samples. A total of 41 proteins were differentially expressed between the IgAVN and IgAV groups out of the 440 proteins analyzed. Five differentially abundant proteins, including VEGF R3, ADAM12, TIM-3, IL-12p40, and CEACAM-5, were further validated by semiquantitative immunofluorescence analysis in kidney tissue from independent cohorts. ADAM12, TIM-3, IL-12p40, and CEACAM-5 were expressed in kidney tissue. A linear relationship was observed between the pathological grade of IgAVN and the expression levels of ADAM12 and CEACAM-5. Furthermore, while the prognosis of children with IgAVN may have a linear relationship with CEACAM-5, the results did not indicate a significant statistical difference, which may be related to the sample size. The expression of ADAM12 and CEACAM-5 was positively correlated with the pathological grade. More importantly, we found that CEACAM-5 may be related to the prognosis of IgAVN, which could serve as a significant biomarker for assessing disease severity and monitoring disease progression.

Dent disease 1-linked novel CLCN5 mutations result in aberrant location and reduced ion currents.

Dent disease is a rare renal tubular disease with X-linked recessive inheritance characterized by low molecular weight proteinuria (LMWP), hypercalciuria, and nephrocalcinosis. Mutations disrupting the 2Cl-/1H+ exchange activity of chloride voltage-gated channel 5 (CLCN5) have been causally linked to the most common form, Dent disease 1 (DD1), although the pathophysiological mechanisms remain unclear. Here, we conducted the whole exome capture sequencing and bioinformatics analysis within our DD1 cohort to identify two novel causal mutations in CLCN5 (c.749 G > A, p. G250D, c.829 A > C, p. T277P). Molecular dynamics simulations of ClC-5 homology model suggested that these mutations potentially may induce structural changes, destabilizing ClC-5. Overexpression of variants in vitro revealed aberrant subcellular localization in the endoplasmic reticulum (ER), significant accumulation of insoluble aggregates, and disrupted ion transport function in voltage clamp recordings. Moreover, human kidney-2 (HK-2) cells overexpressing either G250D or T277P displayed higher cell-substrate adhesion, migration capability but reduced endocytic function, as well as substantially altered transcriptomic profiles with G250D resulting in stronger deleterious effects. These cumulative findings supported pathogenic role of these ClC-5 mutations in DD1 and suggested a cellular mechanism for disrupted renal function in Dent disease patients, as well as a potential target for diagnostic biomarker or therapeutic strategy development.

Blockage of L2HGDH-mediated S-2HG catabolism orchestrates macrophage polarization to elicit antitumor immunity.

The high infiltration of tumor-associated macrophages (TAMs) in the immunosuppressive tumor microenvironment prominently attenuates the efficacy of immune checkpoint blockade (ICB) therapies, yet the underlying mechanisms are not fully understood. Here, we investigate the metabolic profile of TAMs and identify S-2-hydroxyglutarate (S-2HG) as a potential immunometabolite that shapes macrophages into an antitumoral phenotype. Blockage of L-2-hydroxyglutarate dehydrogenase (L2HGDH)-mediated S-2HG catabolism in macrophages promotes tumor regression. Mechanistically, based on its structural similarity to α-ketoglutarate (α-KG), S-2HG has the potential to block the enzymatic activity of 2-oxoglutarate-dependent dioxygenases (2-OGDDs), consequently reshaping chromatin accessibility. Moreover, S-2HG-treated macrophages enhance CD8+ T cell-mediated antitumor activity and sensitivity to anti-PD-1 therapy. Overall, our study uncovers the role of blockage of L2HGDH-mediated S-2HG catabolism in orchestrating macrophage antitumoral polarization and, further, provides the potential of repolarizing macrophages by S-2HG to overcome resistance to anti-PD-1 therapy.

ATP regulates sodium channel kinetics in pancreatic islet beta cells.

Pancreatic beta cells act as glucose sensors, in which intracellular ATP ([ATP](i)) are altered with glucose concentration change. The characterization of voltage-gated sodium channels under different [ATP](i) remains unclear. Here, we demonstrated that increasing [ATP](i) within a certain range of concentrations (2-8 mM) significantly enhanced the voltage-gated sodium channel currents, compared with 2 mM cytosolic ATP. This enhancement was attenuated by even high intracellular ATP (12 mM). Furthermore, elevated ATP modulated the sodium channel kinetics in a dose-dependent manner. Increased [ATP](i) shifted both the current-voltage curve and the voltage-dependent inactivation curve of sodium channel to the right. Finally, the sodium channel recovery from inactivation was significantly faster when the intracellular ATP level was increased, especially in 8 mM [ATP](i), which is an attainable concentration by the high glucose stimulation. In summary, our data suggested that elevated cytosolic ATP enhanced the activity of Na(+) channels, which may play essential roles in modulating ß cell excitability and insulin release when blood glucose concentration increases.

[Investigation on wild resources of Dendrobium officinale distribution and ecological envirment in Anhui].

The wild resources of Dendrobium officinale in Anhui province were studied by textural research, data collection, interview survey and regional survey, in order to investigate the resources distribution and ecological characters and provide the reference for Anhui Dendrobium industry. In this paper, a part of producing areas of wild D. officinale in Anhui province was selected to analyze the ecological characters. As a result, we find that the wild resources of D. officinale in Anhui distributed only sporadic and the conditions of growth environment were harsh. Our findings may provide some suggestions on wild resources protection and artificial cultivation in suitable environments because the wild resources of D. officinale in Anhui are decreasing rapidly and facing an endangered situation.

Risk of cardiac rupture among elderly patients with diabetes presenting with first acute myocardial infarction.

Objective: We aimed to analyze the risk of cardiac rupture (CR) in aged diabetic patients with acute ST-segment elevated myocardial infarction (STEMI) who were followed up for one month, and analyze its independent risk factors. Methods: A total of 3063 aged patients with first onset STEMI admitted to Beijing Anzhen Hospital from January 2001 to December 2020 were retrospectively included. There were 2020 patients without diabetes mellitus (DM) and 1043 patients with DM. We used propensity scores matching (PSM) method to balance baseline exposure factors between patients with or without DM, and all were divided the DM group (1043 cases) and the non-DM group (1043 cases) after the PSM. The primary outcome was CR (the composite rate of papillary muscle rupture, ventricular septum perforation, free wall rupture), which was diagnosed based on clinical manifestations and/or echocardiographic findings. Kaplan-meier survival analyses and log-rank test was used to evaluate the risk of CR between the two groups, and Cox regression analysis was used to evaluate the independent risk factors for CR. Results: After PSM, the baseline clinical data were similar between the DM and non-DM group (all P>0.05). However, level of glycated hemoglobin was significantly higher in the DM group (P<0.05). During 1 month of follow-up, there were 55 (2.64%) cases of CR, most occurred within 48h after admission (40 cases). Among the 55 cases, 11(0.53%) had papillary muscle rupture, 18(0.86%) had ventricular septum perforation, and 26(1.25%) had free wall rupture. Kaplan-meier survival analyses detected that the DM group was associated with significantly increased risk of CR (3.36% vs. 1.92%, HR=1.532, 95% CI: 1.054-2.346, P=0.030), ventricular septum perforation (1.05% vs. 0.67%, HR=1.464, 95% CI: 1.021-2.099, P=0.038) and free wall rupture (1.63% vs. 0.86%, HR=1.861, 95% CI: 1.074-3.225, P=0.027) than those in the non-DM group. Among the 2031 aged STEMI patients without CR, 144 cases (6.90%, 144/2086) died; and among the 55 patients with CR, 37 cases (1.77%, 37/2086) died due to CR. Therefore, twenty percent (20.44%, 37/181) of death was due to CR. Multivariate Cox regression analysis indicated that DM (HR=1.532, 95%CI: 1.054-2.346), age (HR=1.390, 95%CI: 1.079-1.791), female (HR=1.183, 95%CI: 1.049-1.334), troponin I (HR=1.364, 95%CI: 1.108-1.679), brain natriuretic peptide (HR=1.512, 95%CI: 1.069-2.139), revascularization (HR=0.827, 95%CI: 0.731-0.936) and ß-receptor blocker (HR=0.849, 95%CI: 0.760-0.948) were independent risk factors of CR (all P<0.05). Conclusion: DM as well as a few other factors, are independent determinants of CR. CR is not a rare event among the aged STEMI patients and twenty percent of deaths are due to CR. However, large sample-sized studies are warranted to confirm these findings.

Oral delivery of a host-directed antiviral, niclosamide, as a cholate-coated nanoformulation.

Potentially significant drug candidates often face elimination from consideration due to the lack of an effective method for systemic delivery. The poor solubility of these candidates has posed a major obstacle for their development as oral pills or injectables. Niclosamide, a host-directed antiviral, is a good example. In this study, a nanoformulation technology that allows for the non-covalent formulation of niclosamide with cholic acids was developed. This formulation enables efficient systemic delivery through endocytosis and enterohepatic circulation of bile-acid-coated nanoparticles. The oral bioavailability of niclosamide-delivery nanoparticles (NDNs) was significantly enhanced to 38.3%, representing an eight-fold increase compared with pure niclosamide. Consequently, the plasma concentration of niclosamide for the NDN formulation reached 1179.6 ng/mL, which is 11 times higher than the therapeutic plasma level. This substantial increase in plasma level contributed to the complete resolution of clinical symptoms in animals infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). This nanoformulation not only provides an orally deliverable antiviral drug for SARS-CoV-2 with improved pharmaceutical bioavailability, but also offers a solution to the systemic delivery challenges faced by potentially significant drug candidates.

Feasibility and safety of Post-Urgent PCI Same-DaY discharge (PUSDY Trial) in China: protocol for a multicentre randomised controlled trial.

INTRODUCTION: In the Chinese healthcare system, where there is overcrowding in hospitals, especially in tertiary care centres, adoption of same-day discharge (SDD) post-percutaneous coronary intervention (PCI) could potentially lead to significant savings of healthcare resources and costs. This study is a non-inferiority trial examining whether post-PCI SDD is feasible in China. The primary hypothesis is that patient outcomes in post-urgent PCI SDD patients are non-inferior to regular discharge patients. METHODS AND ANALYSIS: Post-Urgent PCI Same-DaY is an investigator-initiated multicentre randomised unblinded clinical non-inferiority trial, with 1:1 centralised randomisation to the SDD or usual care (UC) group. Based on sample size calculations, 1296 patients from at least three hospitals, with mild to moderate myocardial infarction, will be included, and acute coronary syndrome patients will be excluded. All patients will receive UC while patients assigned to the SDD group will be discharged on the same day or within 12 hours post-PCI. The primary outcome is major adverse cardiovascular and cerebrovascular events 30 days after discharge. The secondary outcomes are all-cause mortality, bleeding and access site complications. The outcome rates will be compared between groups with the absolute risk difference with a 95% CI. ETHICS AND DISSEMINATION: The study protocol V.2.0 has been approved on 21 January 2022 by the Ethics Committee of Beijing Anzhen Hospital, Capital Medical University (approval number: 2021 KLSD No. 23). The outcomes of this study will be disseminated through a peer-reviewed journal and presented at international conferences. TRIAL REGISTRATION NUMBER: ChiCTR 2200057065; China Clinical Trial Registration.

A facile synthesis for novel loperamide analogs as potential μ opioid receptor agonists.

A facile synthesis for novel loperamide analogs as potential μ opioid receptors is described. The synthetic procedure for compound 5, which contains two 4-phenyl piperidine scaffolds, was optimized, and this compound was synthesized in excellent yield. We also describe a mild and highly efficient protocol for the synthesis of compounds 6 and 7.