Dementia increases the risk of death in stroke patients: A retrospective cohort-based risk score model study.

BACKGROUND: The relationship between dementia and the mortality of stroke is a significant concern for patients and careers. However, there are few research about it in China and a lack of reliable data on the risk of dementia. We aim to analyze and compare the risk of death in stroke patients with and without dementia. Further investigation into the predictive value of dementia for stroke death. METHODS: All patients with stroke who were identified among residents of Ningxia, between January 1, 2014 to December 31, 2021, set death or May 22, 2022 as the observation endpoint. All patients were screened by 1:4 propensity score matching (PSM). The association between dementia and all-cause mortality was evaluated using Cox regression with survival time. Evaluation of the predictive value of dementia using decision curve analysis (DCA) and clinical impact curve (CIC) curves. RESULT: Mortality of stroke with dementia is 45.4% and without dementia is 13.8%, further calculated one-year mortality is higher in the patients with dementia than without dementia (17.3%vs. 5.4%, p < 0.001). Stroke patients with dementia had a 3.74 times higher risk of death (95% CI = 3.29,4.26) and had a shorter survival time than those without dementia. Dementia was an independent predictor of death in all models (hazard ratio [HR]=3.77,95%CI: 3.31-4.30, p < 0.001). DCA and CIC curves indicated that dementia has a high value in predicting the risk of death in stroke patients. CONCLUSION: Dementia is an independent risk factor for death and reduces survival time in stroke patients.

Ras inhibitor farnesylthiosalicylic acid conjugated with IR783 dye exhibits improved tumor-targeting and altered anti-breast cancer mechanisms in mice.

Ras has long been viewed as a promising target for cancer therapy. Farnesylthiosalicylic acid (FTS), as the only Ras inhibitor has ever entered phase II clinical trials, has yielded disappointing results due to its strong hydrophobicity, poor tumor-targeting capacity, and low therapeutic efficiency. Thus, enhancing hydrophilicity and tumor-targeting capacity of FTS for improving its therapeutic efficacy is of great significance. In this study we conjugated FTS with a cancer-targeting small molecule dye IR783 and characterized the anticancer properties of the conjugate FTS-IR783. We showed that IR783 conjugation greatly improved the hydrophilicity, tumor-targeting and therapeutic potential of FTS. After a single oral administration in Balb/c mice, the relative bioavailability of FTS-IR783 was increased by 90.7% compared with FTS. We demonstrated that organic anion transporting polypeptide (OATP) and endocytosis synergistically drove the uptake of the FTS-IR783 conjugate in breast cancer MDA-MB-231 cells, resulting in superior tumor-targeting ability of the conjugate both in vitro and in vivo. We further revealed that FTS-IR783 conjugate could bind with and directly activate AMPK rather than affecting Ras, and subsequently regulate the TSC2/mTOR signaling pathway, thus achieving 2-10-fold increased anti-cancer therapeutic efficacy against 6 human breast cancer cell lines compared to FTS both in vivo and in vitro. Overall, our data highlights a promising approach for the modification of the anti-tumor drug FTS using IR783 and makes it possible to return FTS back to the clinic with a better efficacy.

Clinical characteristics, outcomes, and risk factors for mortality in patients with cancer and COVID-19 in Hubei, China: a multicentre, retrospective, cohort study.

BACKGROUND: Patients with cancer are a high-risk population in the COVID-19 pandemic. We aimed to describe clinical characteristics and outcomes of patients with cancer and COVID-19, and examined risk factors for mortality in this population. METHODS: We did a retrospective, multicentre, cohort study of 205 patients with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and with a pathological diagnosis of a malignant tumour in nine hospitals within Hubei, China, from Jan 13 to March 18, 2020. All patients were either discharged from hospitals or had died by April 20, 2020. Clinical characteristics, laboratory data, and cancer histories were compared between survivors and non-survivors by use of χ2 test. Risk factors for mortality were identified by univariable and multivariable logistic regression models. FINDINGS: Between Jan 13 and Mar 18, 2020, 205 patients with cancer and laboratory-confirmed SARS-CoV-2 infection were enrolled (median age 63 years [IQR 56-70; range 14-96]; 109 [53%] women). 183 (89%) had solid tumours and 22 (11%) had haematological malignancies. The median duration of follow-up was 68 days (IQR 59-78). The most common solid tumour types were breast (40 [20%] patients), colorectal (28 [14%]), and lung cancer (24 [12%]). 54 (30%) of 182 patients received antitumour therapies within 4 weeks before symptom onset. 30 (15%) of 205 patients were transferred to an intensive care unit and 40 (20%) died during hospital admission. Patients with haematological malignancies had poorer prognoses than did those with solid tumours: nine (41%) of 22 patients with haematological malignancies died versus 31 (17%) of 183 patients with solid tumours (hazard ratio for death 3·28 [95% CI 1·56-6·91]; log rank p=0·0009). Multivariable regression analysis showed that receiving chemotherapy within 4 weeks before symptom onset (odds ratio [OR] 3·51 [95% CI 1·16-10·59]; p=0·026) and male sex (OR 3·86 [95% CI 1·57-9·50]; p=0·0033) were risk factors for death during admission to hospital. INTERPRETATION: Patients with cancer and COVID-19 who were admitted to hospital had a high case-fatality rate. Unfavourable prognostic factors, including receiving chemotherapy within 4 weeks before symptom onset and male sex, might help clinicians to identify patients at high risk of fatal outcomes. FUNDING: National Natural Science Foundation of China.

SPECT imaging of lung ischemia-reperfusion injury using [99mTc]cFLFLF for molecular targeting of formyl peptide receptor 1.

Primary graft dysfunction after lung transplantation, a consequence of ischemia-reperfusion injury (IRI), is a major cause of morbidity and mortality. IRI involves acute inflammation and innate immune cell activation, leading to rapid infiltration of neutrophils. Formyl peptide receptor 1 (FPR1) expressed by phagocytic leukocytes plays an important role in neutrophil function. The cell surface expression of FPR1 is rapidly and robustly upregulated on neutrophils in response to inflammatory stimuli. Thus, we hypothesized that use of [99mTc]cFLFLF, a selective FPR1 peptide ligand, would permit in vivo neutrophil labeling and noninvasive imaging of IRI using single-photon emission computed tomography (SPECT). A murine model of left lung IRI was utilized. Lung function, neutrophil infiltration, and SPECT imaging were assessed after 1 h of ischemia and 2, 12, or 24 h of reperfusion. [99mTc]cFLFLF was injected 2 h before SPECT. Signal intensity by SPECT and total probe uptake by gamma counts were 3.9- and 2.3-fold higher, respectively, in left lungs after ischemia and 2 h of reperfusion versus sham. These values significantly decreased with longer reperfusion times, correlating with resolution of IRI as shown by improved lung function and decreased neutrophil infiltration. SPECT results were confirmed using Cy7-cFLFLF-based fluorescence imaging of lungs. Immunofluorescence microscopy confirmed cFLFLF binding primarily to activated neutrophils. These results demonstrate that [99mTc]cFLFLF SPECT enables noninvasive detection of lung IRI and permits monitoring of resolution of injury over time. Clinical application of [99mTc]cFLFLF SPECT may permit diagnosis of lung IRI for timely intervention to improve outcomes after transplantation.

Single-Photon Emission Computed Tomography Imaging Using Formyl Peptide Receptor 1 Ligand Can Diagnose Aortic Aneurysms in a Mouse Model.

BACKGROUND: Our previous studies showed that neutrophil infiltration and activation plays an important role in the pathogenesis of abdominal aortic aneurysms (AAA). However, there is a lack of noninvasive, inflammatory cell-specific molecular imaging methods to provide early diagnosis of AAA formation. Formyl peptide receptor 1 (FPR1) is rapidly upregulated on neutrophils during inflammation. Therefore, it is hypothesized that the use of cinnamoyl-F-(D)L-F-(D)L-F-K (cFLFLF), a PEGylated peptide ligand that binds FPR1 on activated neutrophils, would permit accurate and noninvasive diagnosis of AAA via single-photon emission computed tomography (SPECT) imaging. MATERIALS AND METHODS: Male C57BL/6 (wild-type) mice were treated with topical elastase (0.4 U/mL type 1 porcine pancreatic elastase) or heat-inactivated elastase (control), and aortic diameter was measured by video micrometry. Comparative histology was performed on Day 14 to assess neutrophil infiltration in aortic tissue. We performed near-infrared fluorescence imaging using c-FLFLF-Cy7 probe on Days 7 and 14 postelastase treatment and measured fluorescence intensity ex vivo in excised aortic tissue. A separate group of animals were injected with 99mTc-c-FLFLF 2 h before SPECT imaging on Day 14 using a SPECT/computed tomography/positron emission tomography trimodal scanner. Coexpression of neutrophils with c-FLFLF was also performed on aortic tissue by immunostaining on Day 14. RESULTS: Aortic diameter was significantly increased in the elastase group compared with controls on Days 7 and 14. Simultaneously, a marked increase in neutrophil infiltration and elastin degradation as well as decrease in smooth muscle integrity were observed in aortic tissue after elastase treatment compared with controls. Moreover, a significant increase in fluorescence intensity of c-FLFLF-Cy7 imaging probe was also observed in elastase-treated mice on Day 7 (approximately twofold increase) and Day 14 (approximately 2.5-fold increase) compared with respective controls. SPECT imaging demonstrated a multifold increase in signal intensity for 99mTc-cFLFLF radiolabel probe in mice with AAA compared with controls on Day 14. Immunostaining of aortic tissue with c-FLFLF-Cy5 demonstrated a marked increase in coexpression with neutrophils in AAA compared with controls. CONCLUSIONS: cFLFLF, a novel FPR1 ligand, enables quantifiable, noninvasive diagnosis and progression of AAAs. Clinical application of this inflammatory, cell-specific molecular probe using SPECT imaging may permit early diagnosis of AAA formation, enabling targeted therapeutic interventions and preventing impending aortic rupture.

The spatiotemporal distribution of human brucellosis in mainland China from 2007-2016.

BACKGROUND: Despite the considerable efforts made to address the issue of brucellosis worldwide, its prevalence in dairy products continues to be difficult to estimate and represents a key public health issue around the world today. The aim of the present study was to better understand the epidemiology of this disease in mainland China. We set out to investigate the yearly spatial distribution and possible hotspots of the disease. METHODS: Human brucellosis data from mainland China between 2007 and 2016 were collected from the China Information System for Disease Control and Prevention. A geographic information system ArcGIS10.3 (ESRI, Redlands) was used to identify potential changes in the spatial and temporal distribution of human brucellosis in mainland China during the study period. These distributions were evaluated using three-dimensional trend analysis and spatial autocorrelation analyse. A gravity-center was used to analyse the migration track of human brucellosis. RESULTS: A total of 399,578 cases of human brucellosis were reported during the 10-year study period. The monthly incidence of brucellosis in China demonstrates clear seasonality. Spring and summer are the peak seasons, while May is the peak month for brucellosis. Three-dimensional trend analysis suggests that brucellosis is on the rise from south to north, and that the epidemic situation in northern China is more severe. Between 2007 and 2016, the overall migration distance of the brucellosis incidence gravity-center was 906.43 km, and the direction was southwest. However, the overall gravity center of brucellosis was still in the northern part of China. In the global autocorrelation analysis, brucellosis in China demonstrated a non-random distribution between 2013 and 2014, with spatial autocorrelation (Z > 1.96, P < 0.05) and a clustering trend, while no clustering trend was found from 2007 to 2012 or from 2015 to 2016. In the local autocorrelation analysis, a Low-Low cluster phenomenon was found in the south of China in 2013 and 2014. CONCLUSION: Human brucellosis remains a widespread challenge, particularly in northern China. The hotspots highlight potential high-risk areas which may require special plans and resources for monitoring and controlling the disease.

Florescence Imaging Lung Cancer with a Small Molecule MHI-148.

MHI-148 is a type of heptamethine cyanine dye that can cross the cytoplasmic membrane of lung cancer cells. Here we tested the cytotoxic, in vivo imaging of MHI-148 in lung-cancer nude mice model. Ex vivo imaging was also been measured by testing the major tissue fluorescence intensity. And, the small molecular compound MHI-148 had low cytotoxicity which could be visualized at 1 h post-injection in tumor. From ex vivo fluorescence imaging, the tumor showed the highest uptake of MHI-148 among all the selected organs expect for the time point of 2 h. MHI-148 could be used for effective imaging in lung cancer tissue with good stability and specificity, which suggested that MHI-148 could be an effective tumor clinical imaging agent.

Sevoflurane promotes migration, invasion, and colony-forming ability of human glioblastoma cells possibly via increasing the expression of cell surface protein 44.

Surgical resection of primary solid tumor under anesthesia remains a common practice. It has been concerned whether general anesthetics, especially volatile anesthetics, may promote the growth, migration, and invasion of cancer cells. In this study, we examined the effects of sevoflurane on human glioblastoma cells and determined the role of cluster of differentiation (CD) 44, a cell surface protein involved in cell growth, migration, and invasion, in sevoflurane's effects. We showed that exposure to 1%-4% sevoflurane did not change the cell proliferation, but concentration-dependently increased the invasion of human glioblastoma U251 cells. Furthermore, 4% sevoflurane significantly increased the migration and colony-forming ability of U251 cells. Similar results were observed in human glioblastoma A172 cells. Exposure to sevoflurane concentration-dependently increased the activity of calpains, a group of cysteine proteinases, and CD44 protein in U251 and A172 cells. Knockdown of CD44 with siRNA abolished sevoflurane-induced increases in calpain activity, migration, invasion, and colony-forming ability of U251 cells. Inhalation of 4% sevoflurane significantly increased the tumor volume and invasion/migration distance of U87 cells from the tumor mass in the nude mice bearing human glioblastoma U87 xenograft in the brain. The aggravation by sevoflurane was attenuated by CD44 silencing. In conclusion, sevoflurane increases the migration, invasion, and colony-forming ability of human glioblastoma cells in vitro, and their tumor volume and invasion/migration in vivo. Sevoflurane enhances these cancer cell biology features via increasing the expression of CD44.

Synthesis and Biological Evaluation of Genistein-IR783 Conjugate: Cancer Cell Targeted Delivery in MCF-7 for Superior Anti-Cancer Therapy.

The flavonoid-based natural product genistein is a biologically active compound possessing promising anti-oxidant and anti-cancer properties. Poor pharmacokinetics along with low potency limit however the therapeutic application of genistein in cancer therapy. In order to overcome those limitations and to expand its therapeutic window of efficacy, we sought to covalently attach genistein with a heptamethine cyanine dye-IR 783-for cancer cell targeting and enhanced delivery to tumors. Herein we report the synthesis, a selective detailed characterization and preliminary in vitro/in vivo biological evaluation of genistein-IR 783 conjugate 4. The conjugate 4 displayed improved potency against human breast cancer MCF-7 cells (10.4 ± 1.0 µM) as compared with the parent genistein (24.8 ± 0.5 µM) or IR 783 (25.7 ± 0.7 µM) and exhibited selective high uptake in MCF-7 as against the normal mammary gland MCF-10A cells in various assays. In the cell viability assay, conjugate 4 exhibited over threefold lower potency against MCF-10A cells (32.1 ± 1.1 µM) suggesting that the anti-cancer profile of parent genistein is significantly improved upon conjugation with the dye IR783. Furthermore, the genistein-IR783 conjugate 4 was shown to be especially accumulated in MCF-7 cancer cells by fluorescent intensity measurements and inverted fluorescence microscopy in fixed cells as well as in live cells with time via live cell confocal fluorescence imaging. The mechanism-based uptake inhibition of conjugate 4 was observed with OATPs inhibitor BSP and in part with amiloride, as a macropinocytosis inhibitor. For the first time we have shown amiloride inhibited uptake of cyanine dye by about ~40%. Finally, genistein-IR 783 conjugate 4 was shown to be localized in MCF-7 tumor xenografts of mice breast cancer model via in vivo near infrared fluorescence (NIRF) imaging. In conclusion, conjugation of genistein with cyanine dye IR783 indeed improved its pharmacological profile by cancer cell selective uptake and targeting and therefore warrants further investigations as a new anti-cancer therapeutics derived from natural product genistein.

Improving Therapeutic Potential of Farnesylthiosalicylic Acid: Tumor Specific Delivery via Conjugation with Heptamethine Cyanine Dye.

The RAS and mTOR inhibitor S-trans-trans-farnesylthiosalicylic acid (FTS) is a promising anticancer agent with moderate potency, currently undergoing clinical trials as a chemotherapeutic agent. FTS has displayed its potential against a variety of cancers including endocrine resistant breast cancer. However, the poor pharmacokinetics profile attributed to its high hydrophobicity is a major hindrance for its continued advancement in clinic. One of the ways to improve its therapeutic potential would be to enhance its bioavailability to cancer tissue by developing a method for targeted delivery. In the current study, FTS was conjugated with the cancer-targeting heptamethine cyanine dye 5 to form the FTS-dye conjugate 11. The efficiency of tumor targeting properties of conjugate 11 against cancer cell growth and mTOR inhibition was evaluated in vitro in comparison with parent FTS. Cancer targeting of 11 in a live mouse model of MCF7 xenografts was demonstrated with noninvasive, near-infrared fluorescence (NIRF) imaging. The results from our studies clearly suggest that the bioavailability of FTS is indeed improved as indicated by log P values and cancer cell uptake. The FTS-dye conjugate 11 displayed higher potency (IC50 = 16.8 ± 0.5 µM) than parent FTS (IC50 = ∼51.3 ± 1.8 µM) and inhibited mTOR activity in the cancer cells at a lower concentration (12.5 µM). The conjugate 11 was shown to be specifically accumulated in tumors as observed by in vivo NIRF imaging, organ distribution, and ex vivo tumor histology along with cellular level confocal microscopy. In conclusion, the conjugation of FTS with cancer-targeting heptamethine cyanine dye improved its pharmacological profile.

The spleen contributes importantly to myocardial infarct exacerbation during post-ischemic reperfusion in mice via signaling between cardiac HMGB1 and splenic RAGE.

The spleen plays a critical role in post-infarct myocardial remodeling. However, the role of the spleen in exacerbating myocardial infarction (MI) during acute ischemia/reperfusion (I/R) injury is unknown. The present study tests the hypothesis that splenic leukocytes are activated by substances released from ischemic myocardium to subsequently exacerbate myocardial injury during reperfusion. The left coronary artery in C57BL/6 mice underwent various durations of occlusion followed by 60 min of reperfusion (denoted as min/min of I/R) with or without splenectomy prior to I/R injury. Splenectomy significantly decreased myocardial infarct size (IS) in 40'/60' and 50'/60' groups (p < 0.05); however, it had no effect on IS in 10'/60', 20'/60' and 30'/60' groups (p = NS). In the 20'/60' group, infusion of 40-min ischemic heart homogenate (40-IHH) upon reperfusion increased IS by >threefold versus infusion of 10-IHH (p < 0.05). Splenectomy abolished the infarct-exacerbating effect of 40-IHH, which was restored by splenic leukocyte adoptive transfer (SPAT). Furthermore, depletion of HMGB1 in the 40-IHH group abolished its infarct-exacerbating effect (p < 0.05), and 40-IHH failed to increase IS in both RAGE(-/-) mice and splenectomized wild-type mice with SPAT from RAGE(-/-) mice. The injection of 40-IHH significantly increased formyl peptide receptor 1 (FPR1) expression in sham spleens when compared to 10-IHH-treated sham and control mice. cFLFLF, a specific FPR1 antagonist, reduced myocardial neutrophil infiltration and abrogated the infarct-exacerbating effect of 40-IHH during reperfusion. A cardio (HMGB1)-splenic (RAGE receptor) signaling axis exists and contributes to myocardial infarct exacerbation during reperfusion after prolonged ischemic insults by activating splenic leukocytes. The FPR1 is a potential therapeutic target for inhibiting the cardio-splenic axis that augments infarct size during post-ischemic reperfusion.

Multimodal formyl peptide receptor 1 targeted inflammation imaging probe: cFLFLF-MHI-DOTA.

Formyl peptide receptor 1 (FPR1) targeting multimodal probe cFLFLFK-MHI-DOTA for leukocyte based inflammation imaging is described. The compound consists of three domains, (a) cFLFLF peptide for FPR1 recognition and binding for activated leukocyte, (b) heptamethine cyanine dye (MHI) for near infrared fluorescence (NIRF) detection and imaging, and (c) metal chelator DOTA ligand that could form complex with a radiometal for nuclear (PET/SPECT) imaging or with a paramagnetic metal for MRI imaging. Detailed synthesis, characterization and in vitro evaluation are reported. The availability of dual mode inflammation imaging probe would allow in vivo gross level imaging of inflammation foci as well as ex vivo microscopic level cellular imaging for role played by innate immune cells in inflamed tissue.

[Expression of the pulmonary surfactant in rat with paraquat-induced acute lung injury].

OBJECTIVE: To explore the expression of pulmonary surfactant in rats with paraquat-induced acute lung injury. METHODS: A total of 36 SD rats were randomly divided into the control group (n=6) and paraquat group at 6, 12, 24, 48, 72 h five time points, each time points 6 rats. All of the rats were injected with paraquat (80 mg/kg) for once. The specimens were collected at 0 h (instant) after paraquat intoxication in the control group, and at the corresponding point in time in the paraquat each time point groups. The pathology changes of lung tissue were observed by HE staining, thiobarbituric acid method was used to detect malondialdehyde (MDA) level, and Western blot method was used to analyze the relative expression of surfactant protein (SP)-A and SP-D in bronchoalveolar lavage fluid (BALF) with time. RESULTS: As compared to control, the levels of MDA in BALF were significantly higher at 6, 24, 48 h after paraquat intoxication ((4.19 ± 0.12), (3.33 ± 0.08), (3.52 ± 0.08) vs (2.82 ± 0.15) nmol/mg, all P<0.01), no significantly different at 12, 72 h ((2.76 ± 0.13), (2.79 ± 0.10) nmol/mg, both P>0.05); the relative expression of SP-A in BALF were significantly higher at 6 h after paraquat intoxication (1.32 ± 0.19 vs 1.00 ± 0.19, P<0.01), lower at 24, 48 h (0.43 ± 0.07, 0.67 ± 0.08, both P<0.01), and no significantly different at 12, 72 h (0.98 ± 0.15, 0.79 ± 0.18, both P>0.05); the relative expression of SP-D in BALF were significantly higher at 6, 12 h after paraquat intoxication (1.54 ± 0.33, 1.64 ± 0.37 vs 1.00 ± 0.23, both P<0.01), no significantly different at 24, 48 h (1.07 ± 0.19, 0.97 ± 0.15, both P>0.05), and reached the peak at 72 h (2.15 ± 0.26, P<0.01); the expression of MDA, SP-A and SP-D were characterized by the state of fluctuation with increased first, reduced after, and finally increased. CONCLUSION: The expression of SP-A, SP-D increase at the early stage of the paraquat-induced acute lung injury in rat, which can reflect the degree of lung injury.

Novel cancer-targeting SPECT/NIRF dual-modality imaging probe (99m)Tc-PC-1007: synthesis and biological evaluation.

Synthesis, characterization, in vitro and in vivo biological evaluation of a heptamethine cyanine based dual-mode single-photon emission computed tomography (SPECT)/near infrared fluorescence (NIRF) imaging probe (99m)Tc-PC-1007 is described. (99m)Tc-PC-1007 exhibited preferential accumulation in human breast cancer MCF-7 cells. Cancer-specific SPECT/CT and NIRF imaging of (99m)Tc-PC-1007 was performed in a breast cancer xenograft model. The probe uptake ratio of tumor to control (spinal cord) was calculated to be 4.02±0.56 at 6 h post injection (pi) and 8.50±1.41 at 20 h pi (P<0.0001). Pharmacokinetic parameters such as blood clearance and organ distribution were assessed.

Increased Incidence and Risk Factors of Infections by Extended-Spectrum ß-Lactamase-Producing Enterobacterales During the COVID-19 Pandemic: A Retrospective Case-Control Study.

Purpose: To investigate changes in the incidence of infections by extended-spectrum ß-lactamase-producing Enterobacterales (ESBL-E) and analyzed whether there was an association between endogenous changes in the organism due to COVID-19 infection and the infections by ESBL-E. Patients and Methods: The study was a single-center retrospective case-control design. A total of 107 patients infected by ESBL-E during the COVID-19 pandemic were selected as the case group, while 214 uninfected patients selected by 1:2 propensity score matching (PSM) acted as the control group. Univariate analysis, LASSO logistic regression, and multivariate logistic regression were used to determine the risk factors for ESBL-E infection. An interrupted time series was used to analyze the changes in the incidence of ESBL-E infections in hospitalized patients during the COVID-19 pandemic. Results: The incidence of infection with ESBL-E showed a significant increase during COVID-19 (3.42 vs 4.92 per 1000 patients, p = 0.003). The incidence of ESBL-E infections increased at an average rate of 0.45 per 1000 patients per week compared to the pre-pandemic period (p = 0.022). Multivariate logistic regression analysis showed that a length of hospitalization ≥ 15 days (OR: 2.98 (1.07-8.28), chronic kidney disease (OR: 4.25 (1.32-13.70), white blood cell (WBC) > 9.5×10^9/L (OR: 3.04 (1.54-6.01), use of hormonal drugs (OR: 2.38 (1.04-5.43), antibacterial drug use 1 type (OR: 5.38 (2.04-14.21), antibacterial drug use 2 types (OR: 23.05 (6.71-79.25) and antibacterial drug use ≥ 3 types (OR: 88.35 (8.55-912.63) were independent risk factors for infection with ESBL-E, while chronic obstructive pulmonary disease (COPD) was a protective factor (OR: 0.14 (0.03-0.66). COVID-19 was not an independent risk factor for infection by ESBL-E. Conclusion: During the COVID-19 pandemic, the incidence of infections by ESBL-E increased significantly. Increased exposure to traditional risk factors were the main reasons, however, COVID-19 was not an independent risk factor for ESBL-E infection.

Multidrug-resistant organisms may be associated with bed allocation and utilization efficiency in healthcare institutions, based on national monitoring data from China (2014-2020).

Analyzing the influence of the bed allocation and utilization efficiency in healthcare institutions on the isolation proportion of Multidrug-resistant organisms (MDROs) to provide data to support prevention and control of MDROs. In this study, the provincial panel data from 2014 to 2020 in China on health resource indicators, including the number of beds per 1,000 population, hospital bed utilization rate, and average hospital stay from 2014 to 2020 in China were used to analyze the relationship between bed allocation or utilization efficiency and MDROs by the panel data quantile regression model. It was shown that the number of beds per 1,000 population had a negative effect on the isolation proportion of methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus faecalis, vancomycin-resistant Enterococcus faecium, penicillin-resistant Streptococcus pneumoniae, methicillin-resistant coagulase-negative Staphylococcus, and cefotaxime or ceftriaxone resistant Escherichia coli (regression coefficient < 0, P < 0.05). The utilization rate of hospital bed had a positive effect on the isolation proportion of methicillin-resistant Staphylococcus aureus, methicillin-resistant coagulase-negative Staphylococcus, vancomycin-resistant Enterococcus faecium, penicillin-resistant Streptococcus pneumoniae, cefotaxime or ceftriaxone resistant Escherichia coli, carbapenem-resistant Escherichia coli, cefotaxime or ceftriaxone resistant Klebsiella pneumoniae, carbapenem-resistant Klebsiella pneumoniae, carbapenem-resistant Pseudomonas aeruginosa, and carbapenem-resistant Acinetobacter baumannii (regression coefficient > 0, P < 0.05). The average hospital stay had a positive effect on the isolation proportion for several antibiotic-resistant organisms, including methicillin-resistant Staphylococcus aureus, methicillin-resistant coagulase-negative Staphylococcus, vancomycin-resistant Enterococcus faecalis, vancomycin-resistant Enterococcus faecium, penicillin-resistant Streptococcus pneumoniae, cefotaxime or ceftriaxone resistant Escherichia coli, carbapenem-resistant Escherichia coli, quinolone-resistant Escherichia coli, cefotaxime or ceftriaxone resistant Klebsiella pneumoniae, carbapenem-resistant Pseudomonas aeruginosa, and carbapenem-resistant Acinetobacter baumannii (regression coefficient > 0, P < 0.05). Bed allocation and utilization efficiency in healthcare institutions may affect the isolation proportion of MDROs in varying degrees.

A novel near-infrared fluorescence imaging probe for in vivo neutrophil tracking.

The development and validation of a multiscopic near-infrared fluorescence (NIRF) probe, cinnamoyl-F-(D)L-F-(D)L-F-PEG-cyanine7 (cFlFlF-PEG-Cy7), that targets formyl peptide receptor on neutrophils using a mice ear inflammation model is described. Acute inflammation was induced in mice by topical application of phorbol-12-myristate-13-acetate to left ears 24 hours before probe administration. Noninvasive NIRF imaging was longitudinally performed up to 24 hours following probe injection. The in vivo neutrophil-targeting specificity of the probe was characterized by a blocking study with preadministration of excess nonfluorescent peptide cFlFlF-PEG and by an imaging study with a scrambled peptide probe cLFFFL-PEG-Cy7. NIRF imaging of mice injected with cinnamoyl-L-F-F-F-L-PEG-cyanine7 (cFlFlF-PEG-Cy7) revealed that the fluorescence intensity for inflamed left ears was approximately fourfold higher than that of control right ears at 24 hours postinjection. In comparison, the ratios acquired with the scrambled probe and from the blocking study were 1.5- and 2-fold at 24 hours postinjection, respectively. Moreover, a microscopic immunohistologic study confirmed that the NIRF signal of cFlFlF-PEG-Cy7 was associated with activated neutrophils in the inflammatory tissue. With this probe, in vivo neutrophil chemotaxis could be correlatively imaged macroscopically in live animals and microscopically at tissue and cellular levels.

Synthesis of PECAM-1-specific 64Cu PET imaging agent: evaluation of myocardial infarction caused by ischemia-reperfusion injury in mouse.

A PECAM-1 specific PET imaging agent, PECAM-1-Ab-DOTA-(64)Cu, was synthesized by conjugating the anti-mouse PECAM-1 antibody with 2,2',2",2"'-(1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrayl)tetraacetic acid (DOTA) and subsequent labeling with (64)Cu. Positron Emission Tomography (PET) was successfully performed in a mouse model of myocardial infarction (MI) induced by an ischemia/reperfusion (I/R) injury, indicating the elevated expression of PECAM-1.

Critical role of FPR1 in splenocyte migration into brain to worsen inflammation and ischemic brain injury in mice.

Background: Splenocyte contribution to ischemic brain injury has been suggested. It is not known whether this effect is due to systemic action or direct influence in ischemic brain tissues. It is also not known how splenocytes migrate into the brain and worsen neurological outcome after brain ischemia. We determined the role of formyl peptide receptor 1 (FPR1), a receptor expressed in monocytes, in the migration of splenocytes into ischemic brain tissues and the contribution of these splenocytes to ischemic brain injury. Methods: Mice with or without fpr1 knockout were subjected to transient focal brain ischemia. The migration of splenocytes was assessed under in vivo and in vitro conditions. Results: cFLFLF, a FPR1 antagonist, inhibited splenocyte migration into the brain and neuroinflammation after ischemic stroke. cFLFLF improved neurological outcome assessed 24 hours or 28 days after stroke. cFLFLF did not alter blood-brain barrier permeability in the ischemic brain. fpr1-/- mice had an attenuated peripheral monocyte and neutrophil infiltration into the brain, a reduced proinflammatory cytokine level and an improved neurological outcome compared with wild-type mice after brain ischemia. cFLFLF did not affect the proinflammatory cytokine levels in the spleen and brain of fpr1-/- mice after ischemic stroke. Conclusions: These results suggest that FPR1 facilitates splenocyte migration into the brain and proinflammatory cytokine production to worsen neurological outcome after brain ischemia, indicating a direct effect of splenocytes on ischemic brain tissues. Our results support the notion that cFLFLF via blocking FPR1 signaling inhibits those pathological processes and is a potential agent for neuroprotection.

Video-assisted bystander cardiopulmonary resuscitation improves the quality of chest compressions during simulated cardiac arrests: A systemic review and meta-analysis.

BACKGROUND: It remains unclear whether video aids can improve the quality of bystander cardiopulmonary resuscitation (CPR). AIM: To summarize simulation-based studies aiming at improving bystander CPR associated with the quality of chest compression and time-related quality parameters. METHODS: The systematic review was conducted according to the PRISMA guidelines. All relevant studies were searched through PubMed, EMBASE, Medline and Cochrane Library databases. The risk of bias was evaluated using the Cochrane collaboration tool. RESULTS: A total of 259 studies were eligible for inclusion, and 6 randomised controlled trial studies were ultimately included. The results of meta-analysis indicated that video-assisted CPR (V-CPR) was significantly associated with the improved mean chest compression rate [OR = 0.66 (0.49-0.82), P < 0.001], and the proportion of chest compression with correct hand positioning [OR = 1.63 (0.71-2.55), P < 0.001]. However, the difference in mean chest compression depth was not statistically significant [OR = 0.18 (-0.07-0.42), P = 0.15], and V-CPR was not associated with the time to first chest compression compared to telecommunicator CPR [OR = -0.12 (-0.88-0.63), P = 0.75]. CONCLUSION: Video real-time guidance by the dispatcher can improve the quality of bystander CPR to a certain extent. However, the quality is still not ideal, and there is a lack of guidance caused by poor video signal or inadequate interaction.