Trends by age and sex and projections of disease prevalence from studying hypertensive heart disease in China over the past three decades.

BACKGROUND: Hypertensive heart disease (HHD) is a common cause of cardiovascular disease and mortality worldwide, and its burden is increasing with aging populations. OBJECTIVES: This study aimed to estimate the prevalence and mortality rates of HHD in mainland China and Taiwan Province using data from the Global Burden of Disease Study 2019 (GBD 2019), and forecast the development trend of HHD from 2020 to 2024. METHODS: We obtained data on number of cases, deaths, crude prevalence rate, crude death rate, age-standardized prevalence rate (ASPR), and age-standardized death rate (ASDR) for mainland China and Taiwan Province from 1990 to 2019 from the GBD 2019. Joinpoint software was used to estimate average annual percentage change (AAPC) with 95% confidence intervals, and the number of HHD cases in China from 2022 to 2024 was predicted by the exponential smoothing method. RESULTS: Between 1990 and 2019, HHD cases and deaths increased in mainland China, but the ASPR and ASDR decreased by 5.96% and 48.72%, respectively. In Taiwan Province, ASPR and ASDR decreased by 7.66% and 52.14%, respectively. The number of HHD cases and death rates varied by region, age, and sex, with a higher number of cases in mainland China than in Taiwan Province. By 2024, the number of HHD cases in mainland China was projected to be over 9.6 million cases, and in Taiwan Province, it was projected to surpass 120,000 cases. CONCLUSION: The differences in HHD cases between mainland China and Taiwan Province in terms of age and sex indicated the need for effective prevention and control measures, especially targeting the elderly population. These findings can inform policymakers and health professionals in the development of targeted prevention and treatment strategies and resource allocation for HHD in China.

Testing for stationary of housing prices in China: An examination using efficient unit root tests.

Changes in housing prices affect all aspects of production and life, and have always been a hot spot of social concern. This paper uses the sequence panel selection method (SPSM) to study the time series properties of housing prices in 100 cities in China from June 2010 to December 2022. It is found that there are large differences in the stationary of housing prices in first/second/third-tier cities. Using the SPSM test method, it is found that housing prices in first-tier cities are all non-stationary series, the samples of second- and third-tier cities can be significantly divided into stable housing prices and non-stable housing prices. After further using the Fourier function to approximate the structural mutation of the data, more second-tier cities show stable housing prices, while less third-tier cities show stable housing prices. These findings provide an important decision-making basis for the government to implement regulatory policies according to local conditions based on the differential characteristics of changes in housing prices.

A novel risk model based on white blood cell-related biomarkers for acute kidney injury prediction in patients with ischemic stroke admitted to the intensive care unit.

Background: Conventional systemic inflammatory biomarkers could predict prognosis in patients with ischemic stroke (IS) admitted to the intensive care unit (ICU). Acute kidney injury (AKI) is common in patients with IS admitted to ICU, but few studies have used systemic inflammatory biomarkers to predict AKI in critically ill patients with IS. This study aimed to establish a risk model based on white blood cell (WBC)-related biomarkers to predict AKI in critically ill patients with IS. Methods: Data were extracted from the Medical Information Mart for Intensive Care-IV (MIMIC-IV) for a training cohort, and data were extracted from the Medical Information Mart for eICU Collaborative Research Database (eICU-CRD) for a validation cohort. Logistic regression analysis was used to determine the significant predictors of WBC-related biomarkers on AKI prediction, and a risk model was established based on those significant indicators in multivariate logistic regression. The receiver operating characteristics (ROC) curve was utilized to obtain the best cut-off value of the risk model. The Kaplan-Meier curve was used to evaluate the prognosis-predictive ability of the risk model. Results: The overall incidence of AKI was 28.4% in the training cohort and 33.2% in the validation cohort. WBC to lymphocyte ratio (WLR), WBC to basophils ratio (WBR), WBC to hemoglobin ratio (WHR), and neutrophil to lymphocyte ratio (NLR) could independently predict AKI, and a novel risk model was established based on WLR, WBR, WHR, and NLR. This risk model depicted good prediction performance both in AKI and other clinical outcomes including hemorrhage, persistent AKI, AKI progression, ICU mortality, and in-hospital mortality both in the training set and in the validation set. Conclusion: A risk model based on WBC-related indicators exhibited good AKI prediction performance in critically ill patients with IS which could provide a risk stratification tool for clinicians in the ICU.

Revisit causal nexus between financial development and environmental quality in China: a structural shift panel data analysis.

Climate change is a challenge for all of humanity. Should financial be environmentally responsible? This paper uses the Toda-Yamamoto test and the extended Fourier Toda-Yamamoto test re-examine the relationship between financial development and environmental quality in 31 provinces and municipalities in China during the period 2000-2018. We find that financial development in certain regions has effectively reduced the concentration of PM2.5, which indicates that it has a significantly positive effect on environmental quality, though with regional differences. After considering structural shifts, the relationship between financial development and environmental improvement is found to be significant in more regions, indicating that China has undergone structural shifts in these aspects. The aforementioned conclusions are also supported by further robustness tests. China can consequently utilize the positive impact of finance for advocating carbon emission reduction and improving environment quality, therefore contributing to the response to global climate change.

The antithrombosis effect of dehydroandrographolide succinate: in vitro and in vivo studies.

CONTEXT: Dehydroandrographolide succinate (DAS) is mainly used in the clinical treatment of various infectious diseases. Its potential effects on platelet aggregation and blood coagulation systems have not been reported systematically. OBJECTIVE: To explore whether DAS exerts an antithrombotic effect and its internal mechanism. MATERIALS AND METHODS: Human blood samples and Sprague-Dawley (SD) rats divided into control, aspirin (30 mg/kg), and DAS groups (200, 400 and 600 mg/kg) were used to measure the platelet aggregation rate, coagulation function, coagulation factor activity, and contents of thromboxane B2 (TXB2) and 6-keto-prostaglandin F1α (6-keto-PGF1α). The histopathology of the SD rat gastric mucosa was also observed. All rats were administered intragastric or intraperitoneal injections once a day for 3 consecutive days. RESULTS: Compared to control group, DAS significantly inhibited the platelet aggregation rate (ED50 = 386.9 mg/kg) by decreasing TXB2 levels (1531.95 ± 649.90 pg/mL to 511.08 ± 411.82 pg/mL) and activating antithrombin III (AT-III) (103.22 ± 16.22% to 146.46 ± 8.96%) (p < 0.05). In addition, DAS significantly enhanced the coagulation factors FV (304.12 ± 79.65% to 443.44 ± 75.04%), FVII (324.19 ± 48.03% to 790.66 ± 225.56%), FVIII (524.79 ± 115.47% to 679.92 ± 143.34%), FX (34.90 ± 7.40% to 102.76 ± 29.41%) and FXI (38.12 ± 10.33% to 65.47 ± 34.08%), increased the content of Fg (2.18 ± 0.39 to 3.61 ± 0.37 g/L), shorten the PT (10.42 ± 0.44 to 9.22 ± 0.21 s), APTT (16.43 ± 1.4 to 14.07 ± 0.75 s) and TT time (37.04 ± 2.13 to 32.68 ± 1.29 s) (p < 0.05), while the aspirin group showed no such effect on these items but showed reduced activity of FII (89.21 ± 21.72% to 61.83 ± 8.95%) and FVIII (524.79 ± 115.47% to 306.60 ± 29.96%) (p < 0.05). Histopathological changes showed aspirin-induced gastric mucosa haemorrhage and the protective effect of DAS in the gastric mucosa. CONCLUSIONS: DAS is more suitable than aspirin in thromboprophylaxis treatment, which provides a reliable theoretical and experimental basis for its clinical application.

CD38 deficiency up-regulated IL-1ß and MCP-1 through TLR4/ERK/NF-κB pathway in sepsis pulmonary injury.

As a disease with high mortality, many cytokines and signaling pathways are associated with sepsis. The pro-inflammatory cytokines and chemokines are participating in the pathogenesis of sepsis, especially in early stage. Moreover, the releases and expressions of cytokines are regulated by numerous signaling pathways, including TLR4/ERK pathway. But despite many studies have expounded the pathogenesis of sepsis and the regulation of cytokines in sepsis, how CD38 influence the expressions of related molecules in sepsis are still unknown. The aim of this study is illuminating the alteration of cytokines and signaling pathways in CD38-/- mice injected with Escherichia coli. Compared with WT mice, E. coli infection results in more severe pulmonary injuries and higher mRNA expressions of cytokines. Compared with E. coli infected WT mice, CD38 knockout leads to aggravated pulmonary injury, increased phosphorylated ERK1/2, p38 and NF-κB p65, and enhanced levels of IL-1ß, iNOS and MCP-1. While compared with E. coli infected CD38-/- mice, TLR4 mutation results in alleviated pulmonary injury, down-regulated phosphorylated ERK1/2 and NF-κB p65, and decreased expressions of IL-1ß and MCP-1. CD38 deficiency increased the expressions of IL-1ß andMCP-1 and aggravated pulmonary injury through TLR4/ERK/NF-κB pathway in sepsis.

TLR4-NLRP3-GSDMD-Mediated Pyroptosis Plays an Important Role in Aggravated Liver Injury of CD38-/- Sepsis Mice.

Clinically, severe bacterial infection can cause septicemia and multiple organ dysfunction syndrome, especially liver injury. CD38 is closely related to many inflammatory pathways, but its role in liver injury caused by bacterial infection remains unclear. The purpose of this study is to discuss the specific role of CD38 in bacterial liver injury. Eight-week-old male C57BL/6 mice (WT, CD38-/- and CD38-/-TLR4mut) were used and stimulated with Escherichia coli (ATCC25922) or PBS, intraperitoneally. After 3 hours of bacterial stimulation, serum was collected to detect ALT and AST concentration, and liver tissue was harvested for hematoxylin and eosin staining and bacterial culture. The mRNA expressions of TLR4, NLRP3, IL-1ß, IL-18, and GSDMD were quantitatively determined by RT-qPCR. The expressions of TLR4, MyD88, TRIF, NF-κB p65, NLRP3, GSDMD, and cytokines were detected by Western blot. The expression and localization of ERK1/2 were detected by immunohistochemistry and Western blot. The results showed that bacterial stimulation could upregulate the expression of inflammatory cytokines, leading to hepatic dysfunction. Moreover, bacterial stimulation of CD38-deficient mice can aggravate the inflammatory response, the expressions of TLR4, NF-κB, and ERK1/2 were significantly increased, and the biomarkers related to pyroptosis also manifested more obvious pyroptosis. However, TLR4 mutation significantly alleviated inflammation and pyroptosis in the liver caused by bacteria, on the basis of CD38 deficiency. Overall, CD38 knockout exacerbates bacteria-induced liver damage through TLR4-NLRP3-GSDMD-mediated pyroptosis.

Electroacupuncture Inhibits Atherosclerosis through Regulating Intestinal Flora and Host Metabolites in Rabbit.

METHODS: In this study, general rabbit conditions, vascular histology, metabolites, and intestinal flora structures were analyzed. Integrated analysis of metabolomics and 16S rRNA sequencing were performed. All the rabbits were randomly divided into four groups. The rabbit model of atherosclerosis was established. The histopathological change in the common carotid artery was assessed by HE staining and the structural change in the flora by 16S rRNA sequencing. HPLC-TOF-MS and Agilent MPP 12.1 were integrated to identify and screen out differential metabolites. Correlational analyses of every differential metabolite with intestinal flora were integrated on Omicshare platform. RESULTS: Atherosclerotic rabbits showed obvious changes in general conditions, significant fibrous cap and necrotic center on carotid artery, abnormal intestinal bacteria structure, and metabolites levels. Electroacupuncture improved the conditions, reduced lipid deposition on the carotid artery wall, diversified intestinal flora, and normalized host metabolism. Integrated analysis showed that 149 altered metabolites were related to 22 intestinal flora, among which eight intestinal floras and 21 metabolites have relationships with atherosclerosis. CONCLUSION: Electroacupuncture can effectively reverse atherosclerosis through manipulating the structural feature of intestinal flora to influence the host metabolites. The possible mechanisms involved activating signal pathways through host metabolites or affecting the activity of cardiovascular-related enzymes, or regulating host lipid metabolism directly.

Tumor-Targeted Gene Silencing IDO Synergizes PTT-Induced Apoptosis and Enhances Anti-tumor Immunity.

Background: Photothermal therapy (PTT) has been demonstrated to be a promising cancer treatment approach because it can be modulated to induce apoptosis instead of necrosis via adjusting irradiation conditions. Recently, an abscopal anti-tumor immunity has been highlighted, in which PTT on the primary tumor also induced repression of distant tumors. In PTT cancer treatments, the mechanism and the role of immune checkpoints to enhance anti-tumor immunity needs to be investigated. Methods: We prepared a multi-functional gold nanorod reagent, GMPF-siIDO, that is composed of gold nanorods (GNRs) that act as the nano-platform and photothermal sensitizer; folic acid (FA) as the tumor-targeting moiety; and IDO-specific RNA (siIDO) as an immune-stimulator functionality for inducing anti-tumor immunity. For this study, we adjusted the irradiation condition of PTT to induce apoptosis and to silence the immune checkpoint indoleamine 2,3 dioxygeonase (IDO), simultaneously. Results: Our studies provide evidence that photothermal effects kill tumor cells mainly via inducing apoptosis, which can significantly improve antitumor immunity when IDO was down-regulated in TME through significant increases of localized CD8+ and CD4+ lymphocytes in tumor tissue, the downregulation of CD8+ and CD4+ lymphocyte apoptosis, and the upregulation of antitumor cytokines, TNF-α and IFN-γ. Conclusion: In this study, we, for the first time, validated the role of IDO as a negative regulator for both PTT-induced tumor cell apoptosis and anti-tumor immunity; IDO is a critical immune checkpoint that impedes PTT while combination of gene knockdown of IDO in TME enhances anti-tumor efficacy of PTT.

TLR2 agonist Pam3CSK4 enhances the antibacterial functions of GM-CSF induced neutrophils to methicillin-resistant Staphylococcus aureus.

A proliferation of studies have demonstrated that the toll-like receptor 2 (TLR2) pathway affects the chemotaxis, phagocytosis, and cytokine release of neutrophils when pathogens invade. Our previous studies have demonstrated that pretreatment with high doses of Pam3CSK4 (>25 µg/ml) improves the antimicrobial activity of neutrophils, however, short-lived neutrophils limit their therapeutic functions. Here, we used granulocyte macrophage-colony stimulating factor (GM-CSF) to generate neutrophils from murine bone marrow, and assessed their effect on the immune response against methicillin-resistant Staphylococcus aureus. As comparing with classical method of generating neutrophils directly from murine bone marrow, our findings show that pretreatment with Pam3CSK4 enhanced the phagocytic and killing activities against MRSA by the GM-CSF induced neutrophils (GM-CSF neutrophils). Chemotaxis of GM-CSF induced neutrophils was significantly increased after the pretreatment with Pam3CSK4. Furthermore, Pam3CSK4 pretreatment enhanced iNOS, CRAMP, TNF-α, IL-1ß, IL-10, and IL-6 expression. Finally, we observed that p38MAPK and Akt phosphorylation kinases were increased significantly in GM-CSF neutrophils pretreatment with Pam3CSK4 in a dose- and time-dependent manner, whereas p38MAPK inhibitor (SB2021190) and PI3K inhibitor (LY294002) attenuated the antimicrobial activities including phagocytosis, killing activity, respiratory burst, and the release of lactoferrin(LTF) by the GM-CSF induced neutrophils. Together, these findings suggest that pretreatment with Pam3CSK4 enhances the antibacterial function of GM-CSF neutrophils against MRSA, and this could be related to the p38MAPK and PI3K signaling pathways.

The Beneficial Effects of Electroacupuncture at PC6 Acupoints (Neiguan) on Myocardial Ischemia in ASIC3 -/- mice.

This study aims to investigate the possible mechanisms of electroacupuncture (EA) at PC6 to improve myocardial ischemia (MI) by regulating the cardiac transient outward potassium current channel (Ito). According to the random number table, the mice were divided into six groups of six mice each: control group, MI group, PC6, LU7 (Lieque-point), ST36 (Zusanli-point), and nonacupoint group. Mice in the control group were injected with saline (20 mg/kg, 24 hours interval), and the other ASIC3 -/- mice were injected subcutaneously twice with isoproterenol (ISO) (20 mg/kg, 24 hours interval). In the preexperiment, 5 mg/kg, 10 mg/kg, 20 mg/kg, and 30 mg/kg of ISO were used, and the results showed that 5 mg/kg and 10 mg/kg of ISO both could induce acute MI, but shorter duration of sustained MI. On the other hand, an injection of 30 mg/kg can make the mice experience arrhythmia or die immediately, and EA was operated at PC6, LU7, ST36 acupoints, and nonacupoint in the mice of PC6, LU7, ST36, and nonacupoint groups, respectively, after injecting twice. Then Western blotting techniques (Western Blot) were used to analyze the protein expressions of Kv1.4, Kv4.2, Kv4.3, and KchIP2. The results of this experiment showed that the protein expressions of Kv1.4, Kv4.2, Kv4.3, and KChIP2 in MI group were significantly lower than those in the control group (p < 0.01). Compared with MI group, the results of PC6, LU7, and ST36 groups obviously increased (p < 0.05). Furthermore, the expressions of PC6 group were higher than LU7 group and ST36 group (p < 0.05). And electrocardiogram's T-waves showed obvious pathological changes in the MI group compared to the control group (p < 0.01). After EA, the abnormal T-waves voltage of ECG in PC6, LU7, and ST36 groups was improved (p < 0.05). In addition, the rate change of PC6 group was larger than that of both LU7 and ST36 groups (p < 0.05). But the T-waves voltage of the nonacupoint group was not significantly different than that of the MI group (p > 0.05).

Nanoscale Mapping and Spectroscopy of Nonradiative Hyperbolic Modes in Hexagonal Boron Nitride Nanostructures.

The inherent crystal anisotropy of hexagonal boron nitride (hBN) provides the ability to support hyperbolic phonon polaritons, that is, polaritons that can propagate with very large wave vectors within the material volume, thereby enabling optical confinement to exceedingly small dimensions. Indeed, previous research has shown that nanometer-scale truncated nanocone hBN cavities, with deep subdiffractional dimensions, support three-dimensionally confined optical modes in the mid-infrared. Because of optical selection rules, only a few of the many theoretically predicted modes have been observed experimentally via far-field reflection and scattering-type scanning near-field optical microscopy (s-SNOM). The photothermal induced resonance (PTIR) technique probes optical and vibrational resonances overcoming weak far-field emission by leveraging an atomic force microscope (AFM) probe to transduce local sample expansion caused by light absorption. Here we show that PTIR enables the direct observation of previously unobserved, dark hyperbolic modes of hBN nanostructures. Leveraging these optical modes and their wide range of angular and radial momenta could provide a new degree of control over the electromagnetic near-field concentration, polarization in nanophotonic applications.

Pretreatment of Pam3CSK4 attenuates inflammatory responses caused by systemic infection of methicillin-resistant Staphylococcus aureus in mice.

Pam3CSK4 is a synthetic tripalmitoylated lipopeptide that acts as a ligand of TLR1/TLR2 by mimicking the acetylated amino terminus of bacterial lipoproteins. Here we found that pretreatment of Pam3CSK4 protected mice from systemic infection of methicillin-resistant Staphylococcus aureus (MRSA), and enhanced the bacterial clearance in bacteremia model. Pro-inflammatory cytokines, such as TNF-α, IL-6, MCP-1 and IFN-γ were significantly decreased in serum from Pam3CSK4-treated mice. Besides, upon PamCSK4 treatment, the TLR2 expression was down-regulated, IRAK1 phosphorylation was inhibited, and the expression of IRAK-M and Tollip, two negative regulators of NF-κB pathway, was up-regulated. All of these indicated that Pam3CSK4 attenuated inflammation via inhibiting TLR1/TLR2 and the downstream NF-κB pathways, and suggested that Pam3CSK4 could be a potential immune modulator for MRSA systemic infection.

Prevalence of human papillomavirus infection among 71,435 women in Jiangxi Province, China.

Cervical cancer is the third most common cancer in women worldwide. Human papillomavirus (HPV) has been identified as an etiological factor for cervical cancer. Data on the prevalence and subtype distribution of HPV infection in Jiangxi Province are incomplete. In this study, we investigated HPV subtype distribution and prevalence in Jiangxi Province between August 1, 2010, and December 31, 2015. A total of 71,435 individuals ranging in age from 16 to 77 years were recruited. Cervicovaginal swabs were collected from each participant, and HPV screening was performed. Our results showed that the HPV prevalence was 22.49% in Jiangxi Province. Overall, 14.99% of individuals were positive for a single HPV type, and 7.49% were positive for multiple types. The most frequently detected low-risk genotypes were HPV-6, and high-risk genotypes were HPV-16, -18, -33, -52, and -58. The prevalence and type distribution of HPV infection exhibits regional and age differences; Yingtan had the highest incidence for high-risk HPV infection (32.00%), and peaks in the frequencies of HPV infections were seen for patients under 20 and over 60 years of age. In conclusion, we present data showing that the HPV prevalence varies significantly with age and regions in Jiangxi Province. These results can serve as valuable reference to guide Jiangxi cervical cancer screening and HPV vaccination programs.

[Effect of Electroacupuncture on ATP-sensitive Potassium Channel and Protein Kinase mRNA Ex- pression in Myocardial Ischemia Model Rats].

Objective To observe the effect of electroacupuncture (EA) at different acupoints on mRNA expressions of ATP-sensitive potassium channel (Kir6. 1, Kir6. 2) and conjugated protein (SUR2A, SUR2B) and protein kinases (PKA, PKG and PKC132) in myocardial ischemia model rats. Methods Myocardial ischemia model was established in healthy male SD rats via subcutaneously injec- ting ISO (85 mg/kg) multipointedly (medial root of limbs and the back). Then they were randomly divided into 4 groups, i.e., the model group, Neiguan (PC6) group, Lieque (LU7) group, non-acupoint group, 10 in each group. Besides, another 10 healthy rats were recruited as the control group. Corresponding EA was performed at respective acupoints to rats in Neiguan (PC6) group, Lieque (LU7) group, non-acu- point group, with dense-sparse wave, 2 -3 mA, 2 -20 Hz, needle retaining time of 20 min, once per day for 7 successive days. mRNA expression levels of Kir6. 1 and Kir6. 2, SUR2A, SUR2B, PKA, PKG, and PKCß2 in left ventricular myocardium were analyzed by Real-time PCR. Results Compared with the con- trol group, mRNA expressions of each index increased in the model group (P <0. 01). Compared with the model group, mRNA expressions of each index significantly decreased in Neiguan (PC6) group and Lieque (LU7) group (P<0. 01). Compared with Neiguan (PC6) group, mRNA expressions of each index significantly increased in Lieque (LU7) group and non-acupoint group (P <0. 01). Compared with Lieque (LU7) group, mRNA expressions of each index significantly increased in non-acupoint group (P <0. 05). Conclusion EA at Neiguan (PC6) could reverse mRNA expression changes of ATP-sensitive potassium channel (Kir6. 1 and Kir6. 2)and conjugated proteins (SUR2A and SUR2B) and protein kinases (PKA, PKG, and PKCß2).

[Tinnitus caused by heart disease and healed from heart].

Tinnitus is recognized as a refractory disease, which is common in clinic, and always treated from the liver and kidney. We treat tinnitus mainly by heart based on syndrome differentiation. It often works well when the left cukou pulse is abnormal. Referring to ancient literature, we find that the heart is related to ears by meridians, and the kidney and heart govern ears. The normal function of heart and kidney means normal hearing. The heart secretes atrial natriuretic polypeptins (ANP), whose receptor is widely distributed in ears and can increase the cochlear blood flow. In this paper we explore the relationship between the heart and the ears so as to provide theories of treatment by heart for tinnitus.

Resonant Enhancement of Second-Harmonic Generation in the Mid-Infrared Using Localized Surface Phonon Polaritons in Subdiffractional Nanostructures.

We report on the strong enhancement of mid-infrared second-harmonic generation (SHG) from SiC nanopillars due to the resonant excitation of localized surface phonon polaritons within the Reststrahlen band. A strong dependence of the SHG enhancement upon the optical mode distribution was observed. One such mode, the monopole, exhibits an enhancement that is beyond what is anticipated from field localization and dispersion of the linear and nonlinear SiC optical properties. Comparing the results for the identical nanostructures made of 4H and 6H SiC polytypes, we demonstrate the interplay of localized surface phonon polaritons with zone-folded weak phonon modes of the anisotropic crystal. Tuning the monopole mode in and out of the region where the zone-folded phonon is excited in 6H-SiC, we observe a further prominent increase of the already enhanced SHG output when the two modes are coupled. Envisioning this interplay as one of the showcase features of mid-infrared nonlinear nanophononics, we discuss its prospects for the effective engineering of nonlinear-optical materials with desired properties in the infrared spectral range.

Control of Methicillin-Resistant Staphylococcus aureus Pneumonia Utilizing TLR2 Agonist Pam3CSK4.

The spread of methicillin-resistant Staphylococcus aureus (MRSA) is a critical health issue that has drawn greater attention to the potential use of immunotherapy. Toll-like receptor 2 (TLR2), a pattern recognition receptor, is an essential component in host innate defense system against S. aureus infection. However, little is known about the innate immune response, specifically TLR2 activation, against MRSA infection. Here, we evaluate the protective effect and the mechanism of MRSA murine pneumonia after pretreatment with Pam3CSK4, a TLR2 agonist. We found that the MRSA-pneumonia mouse model, pretreated with Pam3CSK4, had reduced bacteria and mortality in comparison to control mice. As well, lower protein and mRNA levels of TNF-α, IL-1ß and IL-6 were observed in lungs and bronchus of the Pam3CSK4 pretreatment group. Conversely, expression of anti-inflammatory cytokine IL-10, but not TGF-ß, increased in Pam3CSK4-pretreated mice. Our additional studies showed that CXCL-2 and CXCL1, which are necessary for neutrophil recruitment, were less evident in the Pam3CSK4-pretreated group compared to control group, whereas the expression of Fcγ receptors (FcγⅠ/Ⅲ) and complement receptors (CR1/3) increased in murine lungs. Furthermore, we found that increased survival and improved bacterial clearance were not a result of higher levels of neutrophil infiltration, but rather a result of enhanced phagocytosis and bactericidal activity of neutrophils in vitro and in vivo as well as increased robust oxidative activity and release of lactoferrin. Our cumulative findings suggest that Pam3CSK4 could be a novel immunotherapeutic candidate against MRSA pneumonia.

[Protective effect of pretreatment with TLR2 agonist Pam3Csk4 on mice challenged by methicillin-resistant Staphylococcus aureus].

OBJECTIVE: To evaluate the protective effect of pretreatment with Pam3Csk4, a Toll-like receptor 2 (TLR2) agonist, on mice against methicillin-resistant Staphylococcus aureus (MRSA) infection. METHODS: Kunming mice were injected with Pam3Csk4 (25, 50, 100 µg/mice) via tail vein. 12 and 24 hours later, the mice were inoculated with live MRSA (7×10(10) CFU/kg, ATCC43300) via tail vein. All mice were observed at 2-hour intervals for the first 24 hours and 6-hour intervals for the rest time, and survival was monitored for at least 7 days. Bacterial burden in liver, spleen and kidney of the mice were estimated by colony counting on nutrient agar 6 hours after infection (3×10(8) CFU/mice, ATCC43300). In addition, 6, 12 and 24 hours after MRSA challenge, the concentrations of tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), interferon γ (IFN-γ) and IL-10 were measured by ELISA, and the mRNA levels of these cytokines were detected by fluorescence quantitative PCR (qPCR). Finally, 24 hours after being pretreated with Pam3Csk4, mRNA levels of CXC chemokine ligand 1 (CXCL1) and Fcγ receptor III (FcγRIII) in spleen of the mice were evaluated by qPCR. RESULTS: Compared with normal saline-pretreated mice, we found that mice pretreated with the Pam3Csk4 (100 µg/mice) had higher survival in sepsis models caused by MRSA in dose- and time-dependent manners, and Pam3Csk4 (over 50 µg/mice)-pretreated mice had a survival rate more than 70%. In addition, the protein and mRNA levels of TNFα were markedly reduced in Pam3Csk4-pretreated mice at 6 and 12 hours, but not different from the controls at 24 hours post-infection. While IL-6 at protein and mRNA levels decreased in Pam3Csk4-pretreated mice only at 6 hours post-infection. Both protein and mRNA levels of IFN-γ greatly decreased in Pam3Csk4-pretreated mice compared with those of the control group. However, IL-10 level was unchanged between the two groups at all time points. Further studies showed that the mRNA levels of CXCL1 and FcγRIII were notably raised in spleen of the mice 24 hours after administered with Pam3Csk4 compared with normal saline-pretreated mice. CONCLUSION: Our results suggest that Pam3Csk4 pretreatment can protect mice from challenged by MRSA.

[Effects of Electroacupuncture on Expression of Myocardial Chloride Channel-2 and CLCA Proteins in Mice with Acute Myocardial Ischemia].

OBJECTIVE: To observe the influence of electroacupuncture stimulation (EA) of "Neiguan" (PC 6)/"Lieque" (LU 7) on ST segment of electrocardiogram (ECG) and the expression of myocardiac chloride channel (CLC)-2 and calcium (Ca2+)-activated chloride channel accessory (CLCA) proteins in acute myocardial ischemia (AMI) mice, so as to explore its mechanisms underlying improvement of AMI. METHODS: Thirty ASIC 3-/- knock out mice were randomly divided into control, AMI model, EA-Neiguan (PC 6), EA-Lieque (LU 7) and EA-non-acupoint groups. The AMI model was induced by multiple subcuta-neous injection of isoprenaline (ISO, 0.5 g/L, 20 mg/kg). EA was applied to bilateral PC 6, LU 7, or non-acupoint[the mid-point between "Tianshu" (ST 25) and "Shenque" (CV 8)] for 20 min, once daily for 7 days. The ST segment of ECG of the standard Ⅱlimb-lead was recorded using a PowerLab data acquisition device, the change of myocardial histology observed by using microscope after HE staining, the activity of serum superoxide dismutase (SOD) detected using Colorimetric method, and the expression of CLC-2 and CLCA proteins of the left ventricle myocardium detected by Western blot. RESULTS: Outcomes of HE staining showed that the ischemic injury (sarcoplasm swelling and necrosis, etc.) of the left ventrical myocardial tissue after mo-deling was relatively milder in the EA-PC 6 group, not in the EA-non-acupoint group. The SOD activity was significantly lower in the model group than in the control group (P<0.01), and obviously increased in the EA-PC 6 group(P<0.01), but not in the EA-non-acupoint group (P>0.05). The expression levels of myocardial CLC-2 and CLCA proteins were significantly up-regulated in the model group compared with the control group (P<0.01) and markedly down-regulated in the EA-PC 6 group (not in the EA-non-acupoint group) in comparison with the model group(P<0.01), suggesting a specificity of effects of EA-PC 6 in improving myocardial injury and down-regulating CLC-2 and CLCA protein expression. CONCLUSIONS: EA of "Neiguan" (PC 6) can effectively suppress the increase of expression of CLC-2 and CLCA proteins in the left ventricle myocardium, which may contribute to its effect in relieving myocardial injury in mice.