Effect of Cinnamaldehyde on Systemic Candida albicans Infection in Mice.

OBJECTIVE: To investigate the therapeutic efficacy of cinnamaldehyde (CA) on systemic Candida albicans infection in mice and to provide supportive data for the development of novel antifungal drugs. METHODS: Ninety BALB/c mice were randomly divided into 3 groups according to a random number table: CA treatment group, fluconazole (positive control) group, and Tween saline (negative control) group, with 30 mice in each group. Initially, all groups of mice received consecutive intraperitoneal injections of cyclophosphamide at 200 mg/kg for 2 days, followed by intraperitoneal injection of 0.25 mL C. albicans fungal suspension (concentration of 1.0 × 107 CFU/mL) on the 4th day, to establish an immunosuppressed systemic Candida albicans infection animal model. Subsequently, the mice were orally administered CA, fluconazole and Tween saline, at 240, 240 mg/kg and 0.25 mL/kg respectively for 14 days. After a 48-h discontinuation of treatment, the liver, small intestine, and kidney tissues of mice were collected for fungal direct microscopic examination, culture, and histopathological examination. Additionally, renal tissues from each group of mice were collected for (1,3)- ß -D-glucan detection. The survival status of mice in all groups was monitored for 14 days of drug administration. RESULTS: The CA group exhibited a fungal clearance rate of C. albicans above 86.7% (26/30), significantly higher than the fluconazole group (60.0%, 18/30, P<0.01) and the Tween saline group (30.0%, 9/30, P<0.01). Furthermore, histopathological examination in the CA group revealed the disappearance of inflammatory cells and near-normal restoration of tissue structure. The (1,3)-ß-D-glucan detection value in the CA group (860.55 ± 126.73 pg/mL) was significantly lower than that in the fluconazole group (1985.13 ± 203.56 pg/mL, P<0.01) and the Tween saline group (5910.20 ± 320.56 pg/mL, P<0.01). The mouse survival rate reached 90.0% (27/30), higher than the fluconazole group (60.0%, 18/30) and the Tween saline group (30.0%, 9/30), with a significant difference between the two groups (both P<0.01). CONCLUSIONS: CA treatment exhibited significant therapeutic efficacy in mice with systemic C. albicans infection. Therefore, CA holds potential as a novel antifungal agent for targeted treatment of C. albicans infection.

Predictors of Very Poor Outcome After Mechanical Thrombectomy in Older Patients with Acute Ischemic Stroke.

BACKGROUND: Mechanical thrombectomy (MT) is an effective treatment for patients with acute ischemic stroke due to large vessel occlusion. However, some elderly patients with recanalization have a very poor outcome, including vegetative state and mortality. This study evaluated predictors of very poor outcome at 3 months in older patients with stroke undergoing MT treatment. METHODS: We retrospectively collected data from consecutive stroke patients ≥80 years old undergoing MT between April 2018 and January 2021. A very poor outcome was defined as a modified Rankin Scale (mRS) score of 5 or 6 at 3-month follow-up. Multiple logistic regression analysis was performed to identify the predictors of very poor outcome at 3 months. RESULTS: The study enrolled 62 patients with a median age of 85.5 years (interquartile range: 82.0-89.0). Of patients, 35 (56.5%) had a very poor outcome at 3-month follow-up. Multiple logistic regression analysis identified female sex (odds ratio = 3.592, 95% confidence interval 1.047-12.319, P = 0.042) and stroke-associated pneumonia (odds ratio = 6.103, 95% CI 1.541-24.174, P = 0.010) as independent predictors of very poor outcome. CONCLUSIONS: In elderly stroke patients undergoing MT treatment, female sex and stroke-associated pneumonia were independent predictors of very poor outcome at 3 months.

Efficacy and safety of patient-controlled epidural analgesia versus patient-controlled intravenous analgesia following open hepatectomy: A single-center retrospective study.

Background: Postoperative analgesia is an essential component of enhanced recovery after surgery following abdominal surgery. Studies comparing the effectiveness of epidural analgesia with that of other analgesic modalities after liver surgery have reported inconsistent results. Consequently, the use of epidural analgesia for open hepatectomy is controversial. Objective: The present single-center retrospective study aimed to compare the efficacy and safety of patient-controlled epidural analgesia (PCEA) and patient-controlled intravenous analgesia (PCIA) in adults undergoing open hepatectomy. Methods: Patients who underwent open hepatectomy between January 2018 to December 2019 at Zhongshan Hospital, Fudan University were retrospectively analyzed. Propensity score matching was used to adjust baseline information between the PCEA and PCIA groups. The primary outcome measure was scores of the numeric rating scales (NRSs) for resting, exercise, and nocturnal pain at postoperative 24 h (postoperative day 1 [POD1]) and 48 h (POD2). The secondary outcome indicators included postoperative nausea and vomiting (PONV), hypotension, pruritus, respiratory depression, functional activity score (FAS), effective analgesic pump compression ratio, analgesic relief rate, discontinuation of the analgesic pump, reasons for discontinuation of the analgesic pump, and patient satisfaction with postoperative analgesia. Results: The NRS scores of the PCEA group on POD1 were significantly lower than those of the PCIA group (P < 0.05). On POD2, the difference between the two groups was significant only for motion NRS scores (P < 0.05). The PCIA group had significantly more patients with lower FAS functional class than the PCEA group (P < 0.001). The effective analgesic pump compression ratio and the analgesic relief rate at 2 days after the surgery were lower in the PCEA group than in the PCIA group (P < 0.001). The incidence of pump discontinuation was higher in the PCEA group than in the PCIA group on POD2 (P = 0.044). Moreover, on POD1 and POD2, the PCEA group showed a higher incidence of pruritus and hypotension than the PCIA group (P < 0.001). Both groups showed no significant difference in PONV incidence. Conclusion: In patients undergoing open hepatectomy, PCEA was more effective than PCIA in relieving moderate to severe pain on POD1. However, improving the safety and effectiveness of PCEA remains a challenge.

Red cell distribution width is associated with stroke severity and unfavorable functional outcomes in ischemic stroke.

Background: Red blood cell distribution width (RDW) is considered to be related to coronary heart disease and heart failure and all-cause mortality, but its relationship with acute ischemic stroke is still unclear. In this study, we aimed to explore the relationship between RDW and the stroke severity and functional outcomes of ischemic stroke. Methods: We retrospectively reviewed patients with acute ischemic stroke between September 2016 and January 2020. Demographic, clinical, stroke complications, laboratory data, and treatment were collected for all patients. Stroke severity and functional outcomes were evaluated by NIHSS score, modified Rankin Scale (mRS), and Barthel Index (BI) at 3 months. Furthermore, multiple logistic regression analysis was used to assess the relationship between RDW and stroke severity and functional outcomes. Results: A total of 629 patients with acute ischemic stroke were included and were categorized into four groups according to the quartiles of RDW (< 12.4, 12.4-12.9, 13.0-13.4, > 13.4). After multivariable analysis, higher RDW was directly associated with moderate to severe stroke (OR 2.21, 95% CI, 1.30-3.75, P = 0.003), mRS score of 3-6 at 3 months (OR 1.86, 95% CI, 1.02-3.41, P = 0.044), and BI score below 85 at 3 months (OR 2.27, 95% CI, 1.25-4.12, P = 0.007) in patients with ischemic stroke. Conclusion: Our results demonstrate that RDW is associated with stroke severity and unfavorable functional outcomes at 3 months in patients with ischemic stroke.

High Eckardt score and previous treatment were associated with poor postperoral endoscopic myotomy pain control: A retrospective study.

BACKGROUND: Peroral endoscopic myotomy (POEM) is a safe and effective endoscopic treatment for achalasia. However, postoperative pain management for these patients is often neglected by anesthesiologists because of the short operative time, short hospital stay and the minimally invasive nature of the procedure. AIM: To assess the pain and sleep quality of achalasia patients receiving the POEM procedure and investigate factors that affect postoperative pain. METHODS: This observational study included patients with achalasia who underwent POEM at Zhongshan Hospital from December 2017 to March 2018. General anesthesia was performed with endotracheal intubation. The postoperative visual analog scale (VAS), postoperative sleep quality, basic patient information, and surgical parameters were collected. Depending on whether the 12-h post-POEM VAS score was less than 4, patients were divided into two groups, a well-controlled pain group and a poorly controlled pain group. Univariate, multivariate, and stepwise logistic regression analyses were used to investigate risk factors for poor pain control. A prediction model of post-POEM pain risk was established in the form of a nomogram. The calibration curve and receiver operating characteristic curve were used to evaluate the clinical usage of the prediction model. Repeated measures analysis of variance and simple effect analysis were used to verify whether differences in the VAS and sleep scores of the high- and low-risk groups, divided by the model from the raw data, were statistically significant. RESULTS: A total of 45 eligible patients were included. Multivariate logistic regression and further stepwise logistic regression analysis found that the preoperative Eckardt score [odds ratio (OR): 1.82, 95% confidence interval (CI): 1.17-2.84, P < 0.001], previous treatment (OR: 7.59, 95%CI: 1.12-51.23, P = 0.037) and the distance between the end of the muscle incision and the cardia (OR: 1.52, 95%CI: 0.79-293.93, P = 0.072) were risk factors for post-POEM pain. Repeated measures analysis of variance demonstrated that VAS (P = 0.0097) and sleep scores (P = 0.043) were higher in the high-risk group, and the interactions between the two main effects were obvious (VAS score: P = 0.019, sleep score: P = 0.035). Further simple effect analysis found that VAS scores were higher in the high-risk group at 2 h, 6 h and 12 h (P = 0.005, P = 0.019, P < 0.001), and sleep scores were higher in the high-risk group at day 1 (P = 0.006). CONCLUSION: Achalasia patients who underwent POEM experienced serious postoperative pain, which may affect sleep quality. A higher Eckardt score, previous treatment, and a longer distance between the muscle incision ending and the cardia were risk factors for poor post-POEM pain control.

Dipole Switching by Intramolecular Electron Transfer in Single-Molecule Magnetic Complex [Mn12O12(O2CR)16(H2O)4].

We study intramolecular electron transfer in the single-molecule magnetic complex [Mn12O12(O2CR)16 (H2O)4] for R = -H, -CH3, -CHCl2, -C6H5, and -C6H4F ligands as a mechanism for switching of the molecular dipole moment. Energetics is obtained using the density functional theory (DFT) with onsite Coulomb energy correction (DFT + U). Lattice distortions are found to be critical for localizing an extra electron on one of the easy sites on the outer ring in which localized states can be stabilized. We find that the lowest-energy path for charge transfer is for the electron to go through the center via superexchange-mediated tunneling. The energy barrier for such a path ranges from 0.4 to 54 meV depending on the ligands and the isomeric form of the complex. The electric field strength needed to move the charge from one end to the other, thus reversing the dipole moment, is 0.01-0.04 V/Å.

Enhancing the Catalytic Performance of Candida antarctica Lipase B by Chemical Modification With Alkylated Betaine Ionic Liquids.

Various betaine ionic liquids composed of different chain lengths and different anions were designed and synthesized to modify Candida antarctica lipase B (CALB). The results showed that the catalytic activity of all modified lipases improved under different temperature and pH conditions, while also exhibiting enhanced thermostability and tolerance to organic solvents. With an increase in ionic liquid chain length, the modification effect was greater. Overall, CALB modified by [BetaineC16][H2PO4] performed best, with the modified CALB enzyme activity increased 3-fold, thermal stability increased 1.5-fold when stored at 70°C for 30 min, with tolerance increased 2.9-fold in 50% DMSO and 2.3-fold in 30% mercaptoethanol. Fluorescence and circular dichroism (CD) spectroscopic analysis showed that the introduction of an ionic liquid caused changes in the microenvironment surrounding some fluorescent groups and the secondary structure of the CALB enzyme protein. In order to establish the enzyme activity and stability change mechanisms of the modified CALB, the structures of CALB modified with [BetaineC4][Cl] and [BetaineC16][Cl] were constructed, while the reaction mechanisms were studied by molecular dynamics simulations. Results showed that the root mean square deviation (RMSD) and total energy of modified CALB were less than those of native CALB, indicating that modified CALB has a more stable structure. Root mean square fluctuation (RMSF) calculations showed that the rigidity of modified CALB was enhanced. Solvent accessibility area (SASA) calculations exhibited that both the hydrophilicity and hydrophobicity of the modified enzyme-proteins were improved. The increase in radial distribution function (RDF) of water molecules confirmed that the number of water molecules around the active sites also increased. Therefore, modified CALB has enhanced structural stability and higher hydrolytic activity.

Nomogram to predict 3-month unfavorable outcome after thrombectomy for stroke.

BACKGROUND: Mechanical thrombectomy (MT) is an effective treatment for large-vessel occlusion in acute ischemic stroke, however, only some revascularized patients have a good prognosis. For stroke patients undergoing MT, predicting the risk of unfavorable outcomes and adjusting the treatment strategies accordingly can greatly improve prognosis. Therefore, we aimed to develop and validate a nomogram that can predict 3-month unfavorable outcomes for individual stroke patient treated with MT. METHODS: We analyzed 258 patients with acute ischemic stroke who underwent MT from January 2018 to February 2021. The primary outcome was a 3-month unfavorable outcome, assessed using the modified Rankin Scale (mRS), 3-6. A nomogram was generated based on a multivariable logistic model. We used the area under the receiver-operating characteristic curve to evaluate the discriminative performance and used the calibration curve and Spiegelhalter's Z-test to assess the calibration performance of the risk prediction model. RESULTS: In our visual nomogram, gender (odds ratio [OR], 3.40; 95%CI, 1.54-7.54), collateral circulation (OR, 0.46; 95%CI, 0.28-0.76), postoperative mTICI (OR, 0.06; 95%CI, 0.01-0.50), stroke-associated pneumonia (OR, 5.76; 95%CI, 2.79-11.87), preoperative Na (OR, 0.82; 95%CI, 0.72-0.92) and creatinine (OR, 1.02; 95%CI, 1.01-1.03) remained independent predictors of 3-month unfavorable outcomes in stroke patients treated with MT. The area under the nomogram curve was 0.8791 with good calibration performance (P = 0.873 for the Spiegelhalter's Z-test). CONCLUSIONS: A novel nomogram consisting of gender, collateral circulation, postoperative mTICI, stroke-associated pneumonia, preoperative Na and creatinine can predict the 3-month unfavorable outcomes in stroke patients treated with MT.

Development of a Recombinase-aided Amplification Combined With Lateral Flow Dipstick Assay for the Rapid Detection of the African Swine Fever Virus.

OBJECTIVE: To establish a sensitive, simple and rapid detection method for African swine fever virus (ASFV) B646L gene. METHODS: A recombinase-aided amplification-lateral flow dipstick (RAA-LFD) assay was developed in this study. Recombinase-aided amplification (RAA) is used to amplify template DNA, and lateral flow dipstick (LFD) is used to interpret the results after the amplification is completed. The lower limits of detection and specificity of the RAA assay were verified using recombinant plasmid and pathogenic nucleic acid. In addition, 30 clinical samples were tested to evaluate the performance of the RAA assay. RESULTS: The RAA-LFD assay was completed within 15 min at 37 °C, including 10 min for nucleic acid amplification and 5 minutes for LFD reading results. The detection limit of this assay was found to be 200 copies per reaction. And there was no cross-reactivity with other swine viruses. CONCLUSION: A highly sensitive, specific, and simple RAA-LFD method was developed for the rapid detection of the ASFV.

Effect of Cinnamaldehyde on C. albicans cell wall and (1,3)- ß - D-glucans in vivo.

BACKGROUND: The incidence rate of invasive candidiasis is high, its treatment is difficult, and the prognosis is poor. In this study, an immunosuppressive mouse model of invasive Candida albicans (C. albicans) infection was constructed to observe the effects of cinnamaldehyde (CA) on the C. albicans cell wall structure and cell wall (1,3)-ß-D-glucan contents. This study provides a theoretical basis for CA treatment to target invasive C. albicans infection. METHODS: Immunosuppressed mice with invasive C. albicans infection were given an oral dosage of CA (240 mg.kg- 1.d- 1) for 14 days. Then, mouse lung tissue samples were collected for detection of the levels of (1,3)-ß-D-glucan and transmission electron microscopy observations, using fluconazole as a positive control and 2% Tween 80 saline as a negative control. RESULTS: The immunosuppressive mouse model of invasive C. albicans infection was successfully established. The levels of (1,3)-ß-D-glucan in the CA treatment group, fluconazole positive control group, invasive C. albicans infection immunosuppressive mouse model group, and 2% Tween 80 normal saline control group were 86.55 ± 126.73 pg/ml, 1985.13 ± 203.56 pg/ml, 5930.57 ± 398.67 pg/ml and 83.36 ± 26.35 pg/ml, respectively. Statistically, the CA treatment group, fluconazole positive control group and invasive C. albicans infection immunosuppressive mouse model group were compared with each other (P < 0.01) and compared with the 2% Tween 80 saline group (P < 0.01), showing that the differences were very significant. Comparison of the CA treatment group with the fluconazole positive control group (P < 0.05) displayed a difference as well. Electron microscopy showed that CA destroyed the cell wall of C. albicans, where the outer layer of the cell wall fell off and became thinner and the nuclei and organelles dissolved, but the cell membrane remained clear and intact. CONCLUSION: CA destroys the cell wall structure of C. albicans by interfering with the synthesis of (1,3)-ß-D-glucan to kill C. albicans. However, CA does not affect the cell membrane. This study provides a theoretical basis for CA treatment to target invasive C. albicans infection.

Chemical modification for improving catalytic performance of lipase B from Candida antarctica with hydrophobic proline ionic liquid.

In this study, a series of proline ionic liquids with different lengths of hydrophobic alkyl on the side chain were used to modify the Candida Antarctic lipase B (CALB). The catalytic activity, thermal stability and tolerance to methanol and DMSO of the modified enzyme were all improved simultaneously. The optimum temperature changed from 55 to 60 â„ƒ. The hydrophobicity and anion type of the modifier have important influence on the catalytic performance of CALB. CALB modified by [ProC12][H2PO4] has a better effect. Under the optimal conditions, its hydrolysis activity was 3.0 times than that of the native enzyme, the catalytic efficiency Kcat/Km improved 2.8 times in aqueous phase, and the tolerance to organic solvent with strong polarity (50% methanol 2 h) was increased by 6.8 times. Fluorescence spectra and circular dichroism (CD) spectroscopy showed that the introduction of ionic liquids changed the microenvironment near the fluorophores of the enzyme protein, the α-helix decreased and ß-sheet increased in the secondary structure of the modified enzymes. The root mean square deviation (RMSD), residue root mean square fluctuation (RMSF), radius of gyration (Rg), and solution accessible surface area (SASA) of [ProC2][Br]-CALB, [ProC12][Br]-CALB and native CALB were obtained for comparison by molecular dynamics simulation. The results of dynamics simulation were in good agreement with enzymology experiment. The introduction of ionic liquids can keep CALB in a better active conformation, and proline ionic liquids with long hydrophobic chains can significantly improve the surface hydrophobicity and overall rigidity of CALB. This research offers a new idea for rapid screening of efficient modifiers and provision of enzymes with high stability and activity for industrial application.

Prediction of high-risk esophageal varices in patients with chronic liver disease with point and 2D shear wave elastography: a systematic review and meta-analysis.

OBJECTIVE: To assess the diagnostic performance of liver stiffness (LS) and spleen stiffness (SS) measured by point shear wave elastography (pSWE) and 2D shear wave elastography (2D-SWE) in the detection of high-risk esophageal varices (HREV) and to compare their diagnostic accuracy. METHODS: Through systematic search of PubMed, Embase, and Web of Science databases, we included 17 articles reporting the diagnostic performance of LS or SS measured by pSWE or 2D-SWE for HREV. We used a bivariate random-effects model to estimate pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), area under summary receiver operator characteristic curve (AUSROC), and diagnostic odds ratio (DOR). RESULTS: For LS, there was no significant difference between the pooled sensitivity, 0.89 (95% confidence interval CI, 0.81-0.94) vs. 0.8 (95% CI, 0.72-0.86) (p = 0.13), and specificity, 0.81 (95% CI, 0.73-0.87) vs. 0.73 (95% CI, 0.65-0.79) (p = 0.07) of pSWE and 2D-SWE. The AUSROC and DOR of pSWE were higher than those of 2D-SWE: 0.92 (95% CI, 0.89-0.94) vs. 0.84 (95% CI, 0.80-0.87), p = 0.03, 33 (95% CI, 25-61) vs. 11 (95% CI, 5-22), (p < 0.01). For SS, there was no significant difference between the pooled sensitivity 0.91 (95% CI, 0.78-0.96) vs. 0.89 (95% CI, 0.80-0.94) (p = 0.43); specificity, 0.79 (95% CI, 0.72-0.84) vs. 0.72 (95% CI, 0.63-0.79) (p = 0.06); and DOR, 35 (95% CI, 13-100) vs. 20 (95% CI, 8-50) (p = 0.16) of pSWE and 2D-SWE. CONCLUSION: LS and SS measured by pSWE and 2D-SWE have good accuracy in predicting HREV. KEY POINTS: • There is modest difference between the diagnostic performance of LS and SS measured by pSWE and 2D-SWE. • LS and SS measured by pSWE and 2D-SWE both have high sensitivity, specificity, and AUSROC for the evaluation of HREV in patients with CLD. • pSWE and 2D-SWE are promising tools for noninvasive monitoring risk of esophageal varices bleeding of CLD patients.

Ligand Optimization of Exchange Interaction in Co(II) Dimer Single Molecule Magnet by Machine Learning.

Designing single-molecule magnets (SMMs) for potential applications in quantum computing and high-density data storage requires tuning their magnetic properties, especially the strength of the magnetic interaction. These properties can be characterized by first-principles calculations based on density functional theory (DFT). In this work, we study the experimentally synthesized Co(II) dimer (Co2(C5NH5)4(µ-PO2(CH2C6H5)2)3) SMM with the goal to control the exchange energy, ΔEJ, between the Co atoms through tuning of the capping ligands. The experimentally synthesized Co(II) dimer molecule has a very small ΔEJ < 1 meV. We assemble a DFT data set of 1081 ligand substitutions for the Co(II) dimer. The ligand exchange provides a broad range of exchange energies, ΔEJ, from +50 to -200 meV, with 80% of the ligands yielding a small ΔEJ < 10 meV. We identify descriptors for the classification and regression of ΔEJ using gradient boosting machine learning models. We compare one-hot encoded, structure-based, and chemical descriptors consisting of the HOMO/LUMO energies of the individual ligands and the maximum electronegativity difference and bond order for the ligand atom connecting to Co. We observe a similar overall performance with the chemical descriptors outperforming the other descriptors. We show that the exchange coupling, ΔEJ, is correlated to the difference in the average bridging angle between the ferromagnetic and antiferromagnetic states, similar to the Goodenough-Kanamori rules.

Asymmetric Design of Spin-Crossover Complexes to Increase the Volatility for Surface Deposition.

A mononuclear complex [Fe(tBu2qsal)2] has been obtained by a reaction between an Fe(II) precursor salt and a tridentate ligand 2,4-di(tert-butyl)-6-((quinoline-8-ylimino)methyl)phenol (tBu2qsalH) in the presence of triethylamine. The complex exhibits a hysteretic spin transition at 117 K upon cooling and 129 K upon warming, as well as light-induced excited spin-state trapping at lower temperatures. Although the strongly cooperative spin transition suggests substantial intermolecular interactions, the complex is readily sublimable, as evidenced by the growth of its single crystals by sublimation at 573 → 373 K and ∼10-3 mbar. This seemingly antagonistic behavior is explained by the asymmetric coordination environment, in which the tBu substituents and quinoline moieties appear on opposite sides of the complex. As a result, the structure is partitioned in well-defined layers separated by van der Waals interactions between the tBu groups, while the efficient cooperative interactions within the layer are provided by the quinoline-based moieties. The abrupt spin transition is preserved in a 20 nm thin film prepared by sublimation, as evidenced by abrupt and hysteretic changes in the dielectric properties in the temperature range comparable to the one around which the spin transition is observed for the bulk material. The changes in the dielectric response are in excellent agreement with differences in the dielectric tensor of the low-spin and high-spin crystal structures evaluated by density functional theory calculations. The substantially higher volatility of [Fe(tBu2qsal)2], as compared to a similar complex without tBu substituents, suggests that asymmetric molecular shapes offer an efficient design strategy to achieve sublimable complexes with strongly cooperative spin transitions.

An increase in neutrophil-to-lymphocyte ratio predicts poor functional outcomes in older patients with acute ischemic stroke: a retrospective study.

The neutrophil-to-lymphocyte ratio has emerged as a predictor of functional outcome in stroke patients. However, less is known about the value of neutrophil to lymphocyte ratio in older patients. This clinical study evaluated whether the neutrophil-to-lymphocyte ratio is associated with stroke severity and early clinical outcomes in older patients with acute ischemic stroke. This observational study included acute ischemic stroke patients aged 80 years or older. The patients were divided into three groups, and information was collected, including demographic, clinical and laboratory data. The neutrophil associations to lymphocyte ratio with stroke severity and early clinical outcomes were assessed with logistic regression. Overall, 356 older patients were enrolled in this study, with a median age of 85.0 (82.0-88.0). Split by tertiles of neutrophil-to-lymphocyte ratio, 118 patients were in the bottom tertile (<2.17), 118 patients were in the middle tertile (2.17-3.36), and 120 patients were in the top tertile (>3.36). After multivariable analysis, patients in the highest tertile were likely to have moderate to severe stroke on admission (OR 4.87, 95% CI, 1.93-12.30, P = 0.001), higher risks of primary unfavorable outcome (OR 2.70, 95% CI, 1.09-6.69, P = 0.032) and secondary unfavorable outcome (OR 2.00, 95% CI, 1.00-4.00, P = 0.050) compared to the lowest tertile. Our finding demonstrated that the neutrophil-to-lymphocyte ratio is an independent predictor of stroke severity and early clinical outcomes in older patients with acute ischemic stroke.

Impact of Platelet Endothelial Aggregation Receptor-1 Genotypes on Long-Term Cerebrovascular Outcomes in Patients With Minor Stroke or Transient Ischemic Attack.

Background: Platelet endothelial aggregation receptor-1 (PEAR1) rs12041331 has been reported to affect agonist-stimulated platelet aggregation, but it remains unclear whether this variant plays a role in recurrent stroke. Here we assess the clinical relevance of PEAR1 rs12041331 in acute minor ischemic stroke (AMIS) and transient ischemic attack (TIA) Chinese patients treated with dual antiplatelet therapy (DAPT). Methods: We recruited 273 consecutive minor stroke and TIA patients, and Cox proportional hazard regression was used to model the relationship between PEAR1 rs12041331 and thrombotic and bleeding events. Results: Genotyping for PEAR1 rs12041331 showed 49 (18.0%) AA homozygotes, 129 (47.3%) GA heterozygotes, and 95 (34.7%) GG homozygotes. No association was observed between PEAR1 rs12041331 genotype and stroke or composite clinical vascular event rates (ischemic stroke, hemorrhagic stroke, TIA, myocardial infarction, or vascular death) or bleeding events regardless if individuals carried one or two copies of the A allele. Our results suggested that rs12041331 genetic polymorphism was not an important contributor to clinical events in AMIS and TIA patients in the setting of secondary prevention. Conclusions: Our data do provide robust evidence that genetic variation in PEAR1 rs12041331 do not contribute to atherothrombotic or bleeding risk in minor stroke and TIA patients treated with DAPT.

Stem Cell-Based Therapy for Experimental Ischemic Stroke: A Preclinical Systematic Review.

Stem cell transplantation offers promise in the treatment of ischemic stroke. Here we utilized systematic review, meta-analysis, and meta-regression to study the biological effect of stem cell treatments in animal models of ischemic stroke. A total of 98 eligible publications were included by searching PubMed, EMBASE, and Web of Science from inception to August 1, 2020. There are about 141 comparisons, involving 5,200 animals, that examined the effect of stem cell transplantation on neurological function and infarct volume as primary outcome measures in animal models for stroke. Stem cell-based therapy can improve both neurological function (effect size, -3.37; 95% confidence interval, -3.83 to -2.90) and infarct volume (effect size, -11.37; 95% confidence interval, -12.89 to -9.85) compared with controls. These results suggest that stem cell therapy could improve neurological function deficits and infarct volume, exerting potential neuroprotective effect for experimental ischemic stroke, but further clinical studies are still needed.

Inflammatory markers as independent predictors for stroke outcomes.

BACKGROUND: Inflammation plays an important role in the pathophysiology of stroke. The aim of the present study was to investigate the association between various inflammatory risk markers and ischemic stroke outcome and subtype. METHODS: A total of 3,013 ischemic stroke patients who were admitted to our hospital from 01/01/2016 to 12/30/2018 were retrospectively studied. Stroke subtypes were defined by the Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification. Levels of five common inflammatory markers including white blood cell (WBC) count, neutrophil, lymphocyte, serum C-reactive protein (CRP), and interleukin-6 (IL-6) were measured, and eleven conventional risk factors were further evaluated in the prediction of overall mortality as well as three functional outcomes defined by the National Institute of Health Stroke Scale (NIHSS), the modified Rankin Scale (mRS), and the Barthel Index (BI). Independent predictors of outcome were identified by multivariate logistic regression, and an importance score measured by the area under the receiver operating characteristics curve for each predictor using a Naive Bayes model was reported. RESULTS: Neutrophil and WBC were significantly higher in large-artery atherosclerosis (LAA) and cardioembolism (CE) subtype. In contrast, lymphocyte was significantly higher in small-artery occlusion (SAO). Neutrophil-lymphocyte ratio and CRP level were the best independent predictors, after adjustment for traditional risk factors and TOAST subtype for all four types of outcomes. CONCLUSION: Inflammatory risk markers including neutrophil, lymphocyte, and CRP may have strong independent prediction values for stroke outcome.

The preliminary experience of methylene blue assisted laparoscopy in the treatment of renal parapelvic cysts.

Renal cyst is a common disease in humans and laparoscopic renal cyst decortication is the gold standard for treatment. However, specialized surgical skills are required for the treatment of renal parapelvic cysts. In this study, we describe an improved laparoscopic method for the treatment of renal parapelvic cysts involving the use of continuous infusion of methylene blue. Sixteen patients with renal parapelvic cyst were enrolled in this study. All patients underwent retrograde ureteral catheterization, with continuous perfusion of the renal pelvis using a solution of 0.2% methylene blue and saline, during laparoscopic decortication of the parapelvic cyst. In one patient, the cyst communicated with the renal collection system which was injured, but this was immediately repaired intraoperatively. All operations were successful, and none was converted to open surgery. There were no occurrences of persistent urinary fistula, bleeding, or other complications postoperatively. All patients were followed-up for 3-24 months, and results of postoperative imaging investigations revealed that all of our patients experienced either complete recovery or a greater than 50% decrease in size of the cysts. Our study demonstrates that methylene blue-assisted laparoscopic treatment is a safe, effective and practical method for the treatment of renal parapelvic cysts.

Three Jahn-Teller States of Matter in Spin-Crossover System Mn(taa).

Three high-spin phases recently discovered in the spin-crossover system Mn(taa) are identified through analysis by a combination of first-principles calculations and Monte Carlo simulation as a low-temperature Jahn-Teller ordered (solid) phase, an intermediate-temperature dynamically correlated (liquid) phase, and an uncorrelated (gas) phase. In particular, the Jahn-Teller liquid phase arises from competition between mixing with low-spin impurities, which drive the disorder, and intermolecular strain interactions. The latter are a key factor in both the spin-crossover phase transition and the magnetoelectric coupling. Jahn-Teller liquids may exist in other spin-crossover materials and materials that have multiple equivalent Jahn-Teller axes.