Thromboelastography-guided antiplatelet therapy for patients with ischemic cerebrocardiovascular diseases: a systematic review and meta-analysis.

BACKGROUND: The effectiveness of thromboelastography (TEG)-guided antiplatelet therapy in patients with ischemic cerebrocardiovascular diseases is not well-established. This systematic review evaluates the efficacy and safety of TEG-guided antiplatelet therapy compared to standard treatment in patients with ischemic cerebrocardiovascular diseases. METHODS: Randomized controlled trials (RCTs) and observational studies comparing TEG-guided antiplatelet therapy with standard therapy in patients suffering from ischemic stroke (IS) or coronary artery disease (CAD) were identified. The primary efficacy measure was a composite of ischemic and hemorrhagic events. Secondary efficacy measures included any ischemic events, while safety was assessed by the occurrence of bleeding events. RESULTS: 10 studies involving 4 RCTs and 6 observational studies with a total of 1,678 patients were included. When considering a composite of ischemic and hemorrhagic events in RCTs, a significant reduction was observed in IS or CAD patients under TEG-guided therapy compared to standard therapy (OR 0.45, 95% CI 0.27 to 0.75, P=0.002). After pooling RCTs and observational studies together, compared to standard antiplatelet therapy, TEG-guided therapy significantly reduced the risk of a composite of ischemic and hemorrhagic events (OR 0.26, 95% CI 0.19 to 0.37; P<0.00001), ischemic events (OR 0.28, 95% CI 0.19 to 0.41; P<0.00001), and bleeding events (OR 0.31, 95% CI 0.16 to 0.62; P=0.0009) in patients with IS or CAD. CONCLUSIONS: TEG-guided antiplatelet therapy appears to be both effective and safe for patients with IS or CAD. These findings support the use of TEG testing to tailor antiplatelet therapy in individuals with ischemic cerebrocardiovascular diseases.

Protective effect of exosomes derived from bone marrow mesenchymal stem cells on hypoxia reperfusion injury of cardiomyocytes.

We aimed to investigate the cardiomyocyte-protective effects of bone marrow mesenchymal stem cells (BMSCs)-derived exosomes on ischemia/reperfusion (I/R)-injured rats and to explore the mechanisms. Cardiomyocytes were divided into control group, ischemia/reperfusion group (I/R group), ischemia/reperfusion+exosome group (I/R+Exo group) or ischemia/reperfusion+exosomes transfected with miR-101a-3p inhibitor group (I/R+Exo inhibitor group). MiR-101a-3p levels were lower in I/R and I/R+Exo inhibitor groups than in control and I/R+Exo groups. Apoptosis rate and cleaved caspase 3 expression were higher in I/R and I/R+Exo inhibitor groups. The levels of superoxide dismutase (SOD) in cardiomyocytes of I/R group and I/R+Exo inhibitor group were lower than those of control group and I/R+Exo group, and the levels of malondialdehyde (MDA) and the relative production of oxygen species clusters (ROS) in cardiomyocytes of I/R group and I/R+Exo inhibitor group were higher than those of control group and I/R+Exo group. The levels of interleukin-10 (IL-10), interleukin-6 (IL-6), tumour necrosis factor α (TNF-α), and nuclear factor κB (NF-κB) were higher in the I/R group and the I/R +Exo inhibitor group than in the control group and the I/R+Exo group. Bioinformatics analysis suggested that Pik3c3 is the most promising gene involved in miR-101a-3p-mediated apoptosis in cardiomyocytes, and in vitro experiments confirmed that low expression of miR-101a-3p significantly up-regulated the mRNA and protein expression levels of Pik3c3. BMSCs-derived exosomes have a protective effect on cardiomyocytes from I/R-injured rats, and the mechanism may be related to the inhibition of oxidative stress and inflammatory responses in cardiomyocytes by exosome-delivered miR-101a-3p.

Protective effect of bone marrow mesenchymal stem cell-derived exosomes on cardiomyoblast hypoxia-reperfusion injury through the HAND2-AS1/miR-17-5p/Mfn2 axis.

BACKGROUND: The exosomes (exos) of bone marrow mesenchymal stem cells (BMSCs) play an important therapeutic role in repairing myocardial injury. The purpose of this study was to explore how the exos of BMSCs can alleviate the myocardial cell injury caused by hypoxia/reoxygenation (H/R) through HAND2-AS1/miR-17-5p/Mfn 2 pathway. METHODS: Cardiomyocytes H9c2 were damaged by H/R to mimic myocardial damage. Exos were gained from BMSC. The content of HAND2-AS1 and miR-17-5p was assessed by RT-qPCR. Cell survival rate and apoptosis were estimated by MTT assay and flow cytometry. Western blotting was used to detect the expression of protein. The contents of LDH, SOD, and MDA in the cell culture were detected by commercial kits. The luciferase reporter gene method confirmed the targeted relationships. RESULTS: In H9c2 cells induced by H/R, the level of HAND2-AS1 declined and the expression of miR-17-5p was elevated, but their expression was reversed after exo treatment. Exos improved the cell viability, declined cell apoptosis, controlled the oxidative stress, and repressed inflammation, thus attenuating the damage of H9c2 induced by H/R, whereas, the knockdown of HAND2-AS1 partly alleviated the impacts of exos. MiR-17-5p played the opposite role to HAND2-AS1 on H/R-injured myocardial cells. CONCLUSION: Exos derived from BMSC could alleviate H/R-induced myocardial injury by activating HAND2-AS1/miR-17-5p/Mfn2 pathway.

Polymorphisms of RIG-I-like receptor influence HBV clearance in Chinese Han population.

Retinoic acid-inducible gene I-like receptors (RLRs) play an essential role in human innate immune, which may influence the spontaneous clearance of hepatitis B virus (HBV) infection. We aimed to investigate whether the SNPs in RLR family were associated with HBV spontaneous clearance. The current study included 82 participants with spontaneous clearance, 601 asymptomatic hepatitis B surface antigen (HBsAg) carriers, and 168 participants with chronic hepatitis B (CHB). Six SNPs (DDX58 rs3824456, rs3205166, DHX58 rs2074160, rs2074158, IFIH1 rs2111485, rs3747517) were genotyped to explore their association with HBV spontaneous clearance. Patients carrying the mutant allele C at rs3824456 or A at rs2074160 were more likely to achieve spontaneous clearance compared with asymptomatic HBsAg carriers (additive model: odds ratio [OR] = 0.69, 95% confidence interval [CI] = 0.49-0.97; dominant model: OR = 0.54, 95% CI = 0.31-0.95, respectively). In addition, patients carrying the mutant allele G at rs2111485 were more likely to achieve spontaneous clearance compared with CHB (dominant model: OR = 0.47, 95% CI = 0.25-0.87). The mutations were protective factors for HBV spontaneous clearance. These results suggest the DDX58 rs3824456, DHX58 s2074160, IFIH1 rs2111485 were associated with spontaneous clearance of HBV, which may be predictive markers in the Chinese Han population of HBV.

MicroRNA-34a protects myocardial cells against ischemia-reperfusion injury through inhibiting autophagy via regulating TNFα expression.

BACKGROUND: ischemia-reperfusion (I/R) is a consequence of restored blood supply after myocardial infarction. Myocardial I/R injury can be alleviated by reducing autophagy in heart tissue. MicroRNA-34a (miR-34a) has been shown to regulate autophagy in a renal model of I/R, but it is not known whether it can protect cardiac tissues from I/R injury. This study investigated how miR-34a protects myocardial cells from I/R injury by inhibiting autophagy via regulation of tumor necrosis factor α (TNFα). METHODS: we constructed an I/R model in vivo using Langendorff perfusion, and we constructed an in vivo model by treating neonatal rat cardiomyocytes (NRCMs) with hypoxia-reoxygenation (H/R method). Transfected adenoviral-overexpressed miR-34a mimics and controlled NRCMs after H/R. We analyzed cell viability using the MTT assay and a cell counting kit-8 (CCK-8) assay. Changes in the rate of apoptosis were detected by flow cytometry. We investigated the effect mechanisms of miR-34a with Western blot and luciferase assays. RESULTS: miR-34a expression decreased after in vivo reperfusion of the myocardial cells and heart tissues of neonatal rats. MiR-34a reduced apoptosis of the NRCMs and autophagy levels, simultaneously, after H/R injury. Further, miR-34a decreased the expression of Lc3-II and p62, indicating that miR-34a reduces myocardial I/R injury by decreasing TNFα expression. CONCLUSION: miR-34a can inhibit autophagy levels after I/R by targeting TNFα, thereby reducing myocardial injury.

Antimicrobial susceptibilities of aerobic and facultative gram-negative bacilli isolated from Chinese patients with urinary tract infections between 2010 and 2014.

BACKGROUND: The objective of this study was to investigate the distribution and susceptibility of aerobic and facultative Gram-negative bacilli isolated from Chinese patients with UTIs collected within 48 h (community acquired, CA) or after 48 h (hospital acquired, HA) of hospital admission. METHODS: From 2010 to 2014, the minimum inhibitory concentrations (MICs) of 12 antibiotics for 4,332 aerobic and facultative Gram-negative bacilli, sampled in 21 hospitals in 16 cities, were determined by the broth microdilution method. RESULTS: Enterobacteriaceae composed 88.5% of the total isolates, with Escherichia coli (E. coli) (63.2%) the most commonly isolated species, followed by Klebsiella pneumoniae (K. pneumoniae) (12.2%). Non-Enterobacteriaceae accounted for only 11.5% of all isolates and included mainly Pseudomonas aeruginosa (P. aeruginosa) (6.9%) and Acinetobacter baumannii (A. baumannii) (3.3%). Among the antimicrobial agents tested, the susceptibility rates of E.coli to the two carbapenems, ertapenem and imipenem as well as amikacin and piperacillin-tazobactam ranged from 92.5 to 98.7%. Against K. pneumonia, the most potent antibiotics were imipenem (92.6% susceptibility), amikacin (89.2% susceptibility) and ertapenem (87.9% susceptibility). Although non-Enterobacteriaceae did not show high susceptibilities to the 12 common antibiotics, amikacin exhibited the highest in vitro activity against P. aeruginosa over the 5-year study period, followed by piperacillin-tazobactam, imipenem, ceftazidime, cefepime, ciprofloxacin, and levofloxacin. The Extended Spectrum Beta-Lactamase (ESBL) rates decreased slowly during the 5 years in E. coli from 68.6% in 2010 to 59.1% in 2014, in K. pneumoniae from 59.7 to 49.2%, and in Proteus mirabilis (P. mirabilis) from 40.0 to 26.1%. However, the ESBL rates were different in 5 regions of China (Northeast, North, East, South and Middle-China). CONCLUSION: E. coli and K. pneumonia were the major pathogens causing UTIs and carbapenems and amikacin retained the highest susceptibility rates over the 5-year study period, indicating that they are good drug choices for empirical therapies, particularly of CA UTIs in China.

Update of incidence and antimicrobial susceptibility trends of Escherichia coli and Klebsiella pneumoniae isolates from Chinese intra-abdominal infection patients.

BACKGROUND: To evaluate in vitro susceptibilities of aerobic and facultative Gram-negative bacterial (GNB) isolates from intra-abdominal infections (IAIs) to 12 selected antimicrobials in Chinese hospitals from 2012 to 2014. METHODS: Hospital acquired (HA) and community acquired (CA) IAIs were collected from 21 centers in 16 Chinese cities. Extended spectrum beta-lactamase (ESBL) status and antimicrobial susceptibilities were determined at a central laboratory using CLSI broth microdilution and interpretive standards. RESULTS: From all isolated strains the Enterobacteriaceae (81.1%) Escherichia coli accounted for 45.4% and Klebsiella pneumoniae for 20.1%, followed by Enterobacter cloacae (5.2%), Proteus mirabilis (2.1%), Citrobacter freundii (1.8%), Enterobacter aerogenes (1.8%), Klebsiella oxytoca (1.4%), Morganella morganii (1.2%), Serratia marcescens (0.7%), Citrobacter koseri (0.3%), Proteus vulgaris (0.3%) and others (1.0%). Non- Enterobacteriaceae (18.9%) included Pseudomonas aeruginosa (9.8%), Acinetobacter baumannii (6.7%), Stenotrophomonas maltophilia (0.9%), Aeromonas hydrophila (0.4%) and others (1.1%). ESBL-screen positive Escherichia coli isolates (ESBL+) showed a decreasing trend from 67.5% in 2012 to 58.9% in 2014 of all Escherichia coli isolates and the percentage of ESBL+ Klebsiella pneumoniae isolates also decreased from 2012 through 2014 (40.4% to 26.6%), which was due to reduced percentages of ESBL+ isolates in HA IAIs for both bacteria. The overall susceptibilities of all 5160 IAI isolates were 87.53% to amikacin (AMK), 78.12% to piperacillin-tazobactam (TZP) 81.41% to imipenem (IMP) and 73.12% to ertapenem (ETP). The susceptibility of ESBL-screen positive Escherichia coli strains was 96.77%-98.8% to IPM, 91.26%-93.16% to ETP, 89.48%-92.75% to AMK and 84.86%-89.34% to TZP, while ESBL-screen positive Klebsiella pneumoniae strains were 70.56%-80.15% susceptible to ETP, 80.0%-87.5% to IPM, 83.82%-87.06% to AMK and 63.53%-68.38% to TZP within the three year study. Susceptibilities to all cephalosporins and fluoroquinolones were less than 50% beside 66.5% and 56.07% to cefoxitin (FOX) for ESBL+ Escherichia coli and Klebsiella pneumoniae strains respectively. CONCLUSIONS: The total ESBL+ rates decreased in Escherichia coli and Klebsiella pneumoniae IAI isolates due to fewer prevalence in HA infections. IPM, ETP and AMK were the most effective antimicrobials against ESBL+ Escherichia coli and Klebsiella pneumoniae IAI isolates in 2012-2014 and a change of fluoroquinolone regimens for Chinese IAIs is recommended.

Antimicrobial Susceptibilities of Aerobic and Facultative Gram-Negative Bacilli from Intra-abdominal Infections in Patients from Seven Regions in China in 2012 and 2013.

To evaluate the antimicrobial susceptibility of Gram-negative bacilli that caused hospital-acquired and community-acquired intra-abdominal infections (IAIs) in China between 2012 and 2013, we determined the susceptibilities to 12 antimicrobials and the extended-spectrum ß-lactamase (ESBL) statuses of 3,540 IAI isolates from seven geographic areas in China in a central laboratory using CLSI broth microdilution and interpretive standards. Most infections were caused by Escherichia coli (46.3%) and Klebsiella pneumoniae (19.7%). Rates of ESBL-producing E. coli (P = 0.031), K. pneumoniae (P = 0.017), and Proteus mirabilis (P = 0.004) were higher in hospital-acquired IAIs than in community-acquired IAIs. Susceptibilities of enterobacteriaceae to ertapenem, amikacin, piperacillin-tazobactam, and imipenem were 71.3% to 100%, 81.3% to 100%, 64.7% to 100%, and 83.1% to 100%, respectively, but imipenem was ineffective against P. mirabilis (<20%). Although most ESBL-positive hospital-acquired isolates were resistant to third- and fourth-generation cephalosporins, the majority were susceptible to cefoxitin (47.9% to 83.9%). Susceptibilities of ESBL-positive isolates to ampicillin-sulbactam (<10%) were low, whereas susceptibilities to ciprofloxacin (0% to 54.6%) and levofloxacin (0% to 63.6%) varied substantially. The prevalences of cephalosporin-susceptible E. coli and K. pneumoniae were higher in the northeastern and southern regions than in the central and eastern regions, reflecting the ESBL-positive rates in these areas, and were lowest in the Jiangsu-Zhejiang (Jiang-Zhe) area where the rates of carbapenem resistance were also highest. Ertapenem, amikacin, piperacillin-tazobactam, and imipenem are the most efficacious antibiotics for treating IAIs in China, especially those caused by E. coli or K. pneumoniae. Resistance to cephalosporins and carbapenems is more common in the Jiang-Zhe area than in other regions in China.

On-chip microwave signal generation based on a silicon microring modulator.

A photonic-assisted microwave signal generator based on a silicon microring modulator is demonstrated. The microring cavity incorporates an embedded PN junction that enables a microwave signal to modulate the lightwave circling inside. The DC component of the modulated light is trapped in the cavity, while the high-order sideband components are able to exit the cavity and then generate microwave signals at new frequencies in a photodetector. In our proof-of-concept experiment, a 10 GHz microwave signal is converted to a 20 GHz signal in the optical domain with an electrical harmonic suppression ratio of 22 dB. An analytic model is also established to explain the operation mechanism, which agrees well with the measured data.

Distribution of yeast isolates from invasive infections and their in vitro susceptibility to antifungal agents: evidence from 299 cases in a 3-year (2010 to 2012) surveillance study.

Invasive yeast infections cause significant morbidity and mortality. Surveillance for the infection is necessary to detect trends in species distribution and antifungal resistance. We performed this retrospective study of yeast infection at Jinling Hospital, Nanjing in China, from year of 2010 to 2012. A total of 341 yeast isolates were obtained from patients with invasive infections in the period. Among these isolates, Candida spp. comprised of the highest percentage of yeast strains (91.8 %), followed by Cryptococcus neoformans (5.9 %) and other non-Candida yeast strains (2.3 %). Bloodstream isolates made up 41.3 % of yeast strains and the isolates from CVC made up 17.3 %. Among Candida spp., C. albicans was the most common species identified from non-blood clinical specimens (42.9 %), but appeared in only 20.8 % of blood isolates (P < 0.001). C. tropicalis was the most prevalent Candida species in the blood samples (28.5 %). Candida spp. was mainly isolated from specimens of the ICU patients, while C. neoformans was mainly isolated from specimens in medical wards. Resistance to FLC occurred in 3.7 % of C. albicans, 9.9 % of C. tropicalis, 74.0 % of C. glabrata, and 4.4 % of C. parapsilosis. Most (>92 %) isolates of C. albicans, C. tropicalis, C. parapsilosis, and C. neoformans strains were susceptible to VRC; However, 26.7 % of isolates of C. glabrata were VRC resistant.

Invasive candidiasis in intensive care units in China: in vitro antifungal susceptibility in the China-SCAN study.

OBJECTIVES: The objectives of this study were to determine species distribution and in vitro antifungal susceptibility of Candida isolates identified in the multicentre China-SCAN study of invasive Candida infection (ICI) in intensive care units (ICUs) across China. METHODS: Candida isolates from patients in the China-SCAN study with documented ICI were evaluated by a central laboratory. Species were identified using chromogenic culture media or the API 20C AUX kit. Susceptibility to fluconazole, voriconazole, itraconazole, caspofungin and amphotericin B was determined using the CLSI broth microdilution method (M27-A3) and updated clinical breakpoints or epidemiological cut-off values. RESULTS: A total of 389 isolates from 244 patients were analysed. Species identified most frequently were Candida albicans (40.1%), Candida parapsilosis (21.3%), Candida tropicalis (17.2%) and Candida glabrata (12.9%). Rarer species such as Lodderomyces elongisporus and Candida ernobii were also identified. Fluconazole susceptibility was evident in 85.9% (134/156) of C. albicans, 62.7% (42/67) of C. tropicalis and 48.2% (40/83) of C. parapsilosis isolates. Susceptibility to voriconazole was ≥ 90% among all species. All isolates were susceptible to amphotericin B and caspofungin except C. glabrata [86.0% (43/50) susceptible to caspofungin]. Cross-resistance between fluconazole and voriconazole was observed for C. parapsilosis and C. glabrata. CONCLUSIONS: Although C. albicans was the predominant single species, non-albicans species constituted >50% of isolates. Fluconazole susceptibility was lower in most non-albicans species, indicating that fluconazole resistance should be closely monitored. Susceptibility to voriconazole, amphotericin B and caspofungin is encouraging. Differences between these data and those from other regions emphasize the importance of assessing regional variations.

Heterogeneously integrated III-V/silicon dual-mode distributed feedback laser array for terahertz generation.

We demonstrate an integrated distributed feedback (DFB) laser array as a dual-wavelength source for narrowband terahertz (THz) generation. The laser array is composed of four heterogeneously integrated III-V-on-silicon DFB lasers with different lengths enabling dual-mode lasing tolerant to process variations, bias fluctuations, and ambient temperature variations. By optical heterodyning the two modes emitted by the dual-wavelength DFB laser in the laser array using a THz photomixer composed of an uni-traveling carrier photodiode (UTC-PD), a narrow and stable carrier signal with a frequency of 0.357 THz is generated. The central operating frequency and the emitted terahertz wave linewidth are analyzed, along with their dependency on the bias current applied to the laser diode and ambient temperature.

Dual antiplatelet therapy for ischemic stroke with intracranial arterial stenosis: a systematic review and meta-analysis.

Background: The safety and efficacy of dual antiplatelet therapy (DAPT) in ischemic stroke patients with intracranial artery stenosis (ICAS) remain contentious. Aims: This study evaluates DAPT's effectiveness and safety for these patients. Methods: This review was reported following PRISMA 2020 guidelines. A comprehensive search was conducted in PubMed, Embase, Cochrane Library, ClinicalTrials.gov, CNKI, WanFang, VIP, and SinoMed up to June 20, 2023, for randomized controlled trials comparing efficacy and safety of DAPT against single antiplatelet therapy (SAPT) in ischemic stroke patients with ICAS. The primary outcome was a composite of ischemic and bleeding events. Secondary outcomes included stroke (cerebral infarction and hemorrhage), ischemic events, and cerebral infarction. Safety outcomes assessed were bleeding events, cerebral hemorrhage, and mortality. Risk ratios (RRs) with 95% confidence intervals (CIs) were synthesized using Review Manager 5.4. Results: Analysis of 21 randomized controlled trials involving 3,591 patients revealed that DAPT significantly lowered the rate of ischemic and bleeding events (RR = 0.52; 95% CI: 0.46-0.59, p < 0.001) and recurrent stroke (RR = 0.37; 95% CI: 0.30-0.44, p < 0.001) compared to SAPT. There was no significant increase in bleeding events (RR = 1.34; 95% CI: 0.97-1.85, p = 0.07) or cerebral hemorrhage (RR = 0.47; 95% CI: 0.17-1.31, p = 0.15). Conclusion: DAPT proveed to be effective and safe for ischemic stroke patients with ICAS and significantly reduced stroke and the composite endpoint of ischemic and bleeding events without elevating bleeding risks.

Silicon mode multi/demultiplexer based on multimode grating-assisted couplers.

A simple and low-crosstalk 1 × 4 silicon mode (de)multiplexer based on multimode grating-assisted-couplers is proposed. Mode transitions can be flexibly controlled by designing the grating period at the phase-matching condition. Due to the contra-directional coupling, precise control of the coupling strength and the coupling length are not needed in the system. Calculation results show that the insertion loss and the 3 dB bandwidths of the device are 0.2 dB and 3.7 nm, 0.34 dB and 7.6 nm, and 0.21 dB and 11.8 nm for the channels which (de)multiplex to the 1st, 2nd, and 3rd modes of the bus waveguide, respectively.

FSR-free add-drop filter based on silicon grating-assisted contradirectional couplers.

We propose an add-drop filter with an unlimited free spectral range (FSR). The device is based on grating-assisted contradirectional couplers with silicon-on-insulator ridge waveguides. The intrawaveguide coupling is significantly diminished by distancing the periodically structured corrugated waveguide away from the straight input waveguide. Based on this asymmetric structure, calculated results show that the peak reflectivity of the intrawaveguide coupling is lower than 0.1 dB, while that of the contradirectional coupling is higher than 20 dB. An experimental result of 1.8 dB for the intrawaveguide coupling is obtained. A narrow drop-port bandwidth of 0.8 nm is also achieved experimentally.

Syringin exerts anti-inflammatory and antioxidant effects by regulating SIRT1 signaling in rat and cell models of acute myocardial infarction.

INTRODUCTION: This study aimed to investigate the role of syringin in improving heart function during myocardial ischemia/reperfusion (I/R) and to determine whether the sirtuin 1/peroxisome proliferator-activated receptor gamma coactivator 1 alpha (SIRT1/PGC-1α) pathway contributes to this cardioprotective effect in vivo and in vitro. METHODS: H9c2 cells were incubated with H2 O2 for 12 h. The effect of syringin was assessed by measuring cell viability; the apoptotic rate; Keap1/NRF2/HO-1 activation; and the levels of proinflammatory cytokines, oxidative products, and antioxidative enzymes. In addition, SIRT1 was silenced via short hairpin RNA (shRNA)-SIRT1 transfection to evaluate its involvement in syringin-mediated protection. Syringin rescued cells from H2 O2 -induced reductions in viability, antioxidative enzyme levels, and NRF2/HO-1 activation; likewise, syringin inhibited apoptosis, inflammation, and oxidative stress. We also created a rat model of I/R by ligating the left anterior descending coronary artery for 30 min, followed by reperfusion for 12 min. Syringin was then intraperitoneally injected, and the effect on infarct size and cardiac function was examined after 7 days. NRF2/HO-1 activity and the levels of myocardial proinflammatory cytokines, oxidative products, and antioxidative enzymes were measured. RESULTS: In comparison to the untreated I/R group, the syringin treatment group exhibited improved cardiac function and reduced cardiac lesion and infarct size. Syringin administration also markedly reduced the levels of proinflammatory cytokines and reactive oxygen species and promoted antioxidative enzyme expression and NRF2/HO-1 pathway activation. CONCLUSIONS: Syringin may serve a protective role in animal and cell models of I/R by improving cardiac function, inhibiting the inflammatory response, and activating the antioxidative response.

Network pharmacology-based analysis to explore the therapeutic mechanism of Cortex Dictamni on atopic dermatitis.

ETHNOPHARMACOLOGICAL RELEVANCE: Dermatitis is a common clinical chronic inflammatory skin disease, which incidence has been on the rise in recent years. It not only seriously affects the physical and mental health of patients but also increase economic burden. Currently, commonly used drugs such as corticosteroids, anti-histamines have certain side effects or are expensive. Therefore, the search for an alternative therapy for dermatitis has important clinical significance. Cortex Dictamni is a commonly used traditional Chinese medicine for expelling wind and itching, but its mechanism for treating dermatitis is still unclear. MATERIALS AND METHODS: Network pharmacological analysis was performed to predict the potential targets and pathways of Cortex Dictamni against dermatitis. Molecular docking was used to assess the binding affinity of active compounds and core targets. By repeatedly stimulating the ears with 1-fluoro-2,4-dinitrobenzene (DNFB), an atopic dermatitis (AD) mouse model was established in order to study the anti-dermatitis effect of Cortex Dictamni. The skin thickness and inflammatory cell infiltration in mouse ears were assessed by tissue staining and flow cytometric. The levels of inflammatory factors were detected by enzyme-linked immunosorbent assay (ELISA), and the total protein and phosphorylation levels of related pathways were analyzed by western blotting. RESULTS: In this study, 11 active ingredients, 122 Cortex Dictamni and dermatitis intersection targets were identified. The results from Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that the core targets were mainly enriched in immune response and inflammatory signaling pathways. AD mice treated with ethanol extract of Cortex Dictamni (ECD) improved the symptoms of ear skin lesions, alleviated epidermis and dermis thickening of the AD mice ears, decreased pathological immune cell infiltration and attenuated the levels of inflammatory cytokines (TLR4, IL-6, IL-17), and inhibited the hyperactivation of the PI3K-AKT, JAK1-STAT3/STAT6 signal pathways. CONCLUSIONS: Cortex Dictamni can improve the symptoms of skin lesions and the degree of inflammation caused by AD, and may inhibit AD through multiple pathways, such as regulating PI3K-AKT and JAK1-STAT3/STAT6 pathways. These results not only provide experimental evidence for the clinical application of Cortex Dictamni but also provide some help for the research and development of dermatitis drugs.

A Mouse Ear Model for Allergic Contact Dermatitis Evaluation.

Skin is the human body's first line of defense and one of the most exposed organs to environmental chemicals. Allergic contact dermatitis (ACD) is a common skin disease that manifests as a local rash, redness, and skin lesions. The occurrence and development of ACD are influenced by both genetic and environmental factors. Although many scholars have constructed a series of models of ACD in recent years, the experimental protocols of these models are all different, which makes it difficult for readers to establish them well. Therefore, a stable and efficient animal model is of great significance to further study the pathogenesis of atopic dermatitis. In this study, we detail a modeling method using 1-fluoro-2,4-dinitrobenzene (DNFB) to induce ACD-like symptoms in the ears of mice and describe several methods for assessing the severity of dermatitis during modeling. This experimental protocol has been successfully applied in some experiments and has a certain promotional role in the field of ACD research.

Dictamnine ameliorates chronic itch in DNFB-induced atopic dermatitis mice via inhibiting MrgprA3.

Chronic itch is the most prominent feature of atopic dermatitis (AD), and antihistamine treatment is often less effective in reducing clinical pruritus severity in AD. Multiple studies have shown that histamine-independent itch pathway is thought to predominate in AD-induced chronic itch. Mas-related G-protein-coupled receptor (Mrgpr) A3+ sensory neurons have been identified as one of the major itch-sensing neuron populations, and transient receptor potential (TRP) channel A1 is the key downstream of MrgprA3-mediated histamine-independent itch. MrgprA3-TRPA1 signal pathway is necessary for the development of chronic itch and may be the potentially promising target of chronic itch in AD. Dictamnine is one of the main quinoline alkaloid components of Cortex Dictamni (a traditional Chinese medicine widely used in clinical treatment of skin diseases). However, the anti-inflammatory and anti-pruritic effect of dictamnine on AD have not been reported. In this study, we used the 2,4-dinitrofluorobenzene (DNFB)-induced AD mouse model to observe the scratching behavior, inflammatory manifestations, and to detect the expression of MrgprA3 and TRPA1 in skin and DRG. The data demonstrated that dictamnine effectively inhibited AD-induced chronic itch, inflammation symptoms, epidermal thickening, inflammatory cell infiltration, and downregulated the expression of MrgprA3 and TRPA1. Furthermore, dictamnine restrained the excitability of MrgprA3+ and TRPA1+ neurons. Molecular docking also indicated that dictamnine has better binding affinity with MrgprA3. These results suggest that dictamnine may inhibit chronic itch caused by AD through the MrgprA3-TRPA1 mediated histamine-independent itch pathway, and may have a potential utility in AD treatment.

In vitro susceptibilities of yeast species to fluconazole and voriconazole as determined by the 2010 National China Hospital Invasive Fungal Surveillance Net (CHIF-NET) study.

We conducted active, laboratory-based surveillance for isolates from patients with invasive infections across China from August 2009 to July 2010. DNA sequencing methods were used to define species, and susceptibility to fluconazole and voriconazole was determined by the Clinical and Laboratory Standards Institute M44-A2 disk diffusion method but using up-to-date clinical breakpoints or epidemiological cutoff values. Candida spp. made up 90.5% of the 814 yeast strains isolated, followed by Cryptococcus neoformans (7.7%) and other non-Candida yeast strains (1.7%). Bloodstream isolates made up 42.9% of the strains, isolates from ascitic fluid made up 22.1%, but pus/tissue specimens yielded yeast strains in <5% of the cases. Among the Candida isolates, Candida albicans was the most common species from specimens other than blood (50.1%) but made up only 23% of the bloodstream isolates (P < 0.001). C. parapsilosis complex species were the most common Candida isolates from blood (33.2%). Uncommon bloodstream yeast strains included Trichosporon spp., C. pelliculosa, and the novel species C. quercitrusa, reported for the first time as a cause of candidemia. Most (>94%) of the isolates of C. albicans, C. tropicalis, and the C. parapsilosis complex were susceptible to fluconazole and voriconazole, as were all of the Trichosporon strains; however, 12.2% of the C. glabrata sensu stricto isolates were fluconazole resistant and 17.8% had non-wild-type susceptibility to voriconazole. Seven C. tropicalis strains were cross-resistant to fluconazole and voriconazole; six were from patients in the same institution. Resistance to fluconazole and voriconazole was seen in 31.9% and 13.3% of the uncommon Candida and non-Candida yeast strains, respectively. Causative species and azole susceptibility varied with the geographic region. This study provided clinically useful data on yeast strains and their antifungal susceptibilities in China.