The cGAS-STING pathway in COPD: targeting its role and therapeutic potential.

Chronic obstructive pulmonary disease(COPD) is a gradually worsening and fatal heterogeneous lung disease characterized by airflow limitation and increasingly decline in lung function. Currently, it is one of the leading causes of death worldwide. The consistent feature of COPD is airway inflammation. Several inflammatory factors are known to be involved in COPD pathogenesis; however, anti-inflammatory therapy is not the first-line treatment for COPD. Although bronchodilators, corticosteroids and roflumilast could improve airflow and control symptoms, they could not reverse the disease. The cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) signaling pathway plays an important novel role in the immune system and has been confirmed to be a key mediator of inflammation during infection, cellular stress, and tissue damage. Recent studies have emphasized that abnormal activation of cGAS-STING contributes to COPD, providing a direction for new treatments that we urgently need to develop. Here, we focused on the cGAS-STING pathway, providing insight into its molecular mechanism and summarizing the current knowledge on the role of the cGAS-STING pathway in COPD. Moreover, we explored antagonists of cGAS and STING to identify potential therapeutic strategies for COPD that target the cGAS-STING pathway.

Mapping the hotspots and future trends of electrical stimulation for peripheral nerve injury: A bibliometric analysis from 2002 to 2023.

Peripheral nerve injuries often result in severe personal and social burden, and even with surgical treatment, patients continue to have poor clinical outcomes. Over the past two decades, electrical stimulation has been shown to promote axonal regeneration and alleviate refractory neuropathic pain. The aim of this study was to analyse this field using a bibliometric approach. Literature was searched through Web of Science Core Collection (WOSCC) for the years 2002-2023. Literature analysis included: (1) Describing publication trends in the field. (2) Exploring collaborative network relationships. (3) Finding research advances and research hotspots in the field. (4) Summarizing research trends in the field. With the number of studies in this field still increasing, a total of 693 publications were included in the analysis. This field of research is interdisciplinary in nature. Research hotspots include peripheral nerve regeneration, the treatment of neuropathic pain, materials for nerve injury repair, and the restoration of sensory function in patients with peripheral nerve injury. Correspondingly, the development of nerve conduits and systems for peripheral nerve electrical stimulation, clinical trials of peripheral nerve electrical stimulation, and tactile recovery and movement for amputees have shown significant promise as future research trends in this field.

[Retrospective cross-sectional survey of clinical characteristics and syndrome elements distribution at different stages of coronary heart disease].

The clinical data of coronary heart disease(CHD) patients treated in the First Affiliated Hospital of Guangzhou University of Chinese Medicine and Shenzhen Hospital of Integrated Traditional Chinese and Western Medicine from January 2022 to March 2023 were retrospectively collected. This study involved the descriptive analysis of demographic characteristics, clinical symptoms, and tongue and pulse features. The χ~2 test was conducted to analyze the distribution of syndrome elements and their combinations at diffe-rent stages of CHD, so as to reveal the clinical characteristics and syndrome patterns at various pathological stages of CHD. This study extracted 28 symptom entries, 10 tongue manifestation entries, and 7 pulse manifestation entries, summarized the 5 main disease locations of the heart, lung, liver, spleen, and kidney, and the 8 main disease natures of blood stasis, phlegm turbidity, Qi stagnation, heat(fire), fluid retention, Qi deficiency, Yin deficiency, and Yang deficiency and 8 combinations of disease natures. The χ~2 test showed significant differences in the distribution of syndrome elements including the lung, liver, spleen, kidney, blood stasis, heat(fire), Qi stagnation, heat syndrome, water retention, Qi deficiency, Yin deficiency, and Yang deficiency between different disease stages. Specifically, the liver, blood stasis, heat(fire), and Qi stagnation accounted for the highest proportion during unstable stage, and the lung, spleen, kidney, water retention, Qi deficiency, Yin deficiency, and Yang deficiency accounted for the highest proportion at the end stage. The distribution of Qi deficiency varied in the different time periods after percutaneous coronary intervention(PCI). As shown by the χ~2 test of the syndrome elements combination, the distribution of single disease location, multiple disease locations, single disease nature, double disease natures, multiple natures, excess syndrome, and mixture of deficiency and excess varied significantly at different stages of CHD. Specifically, single disease location, single disease nature, and excess syndrome accounted for the highest proportion during the stable stage, and double disease natures accounted for the highest proportion during the unstable stage. Multiple disease locations, multiple disease natures, and mixture of deficiency and excess accounted for the highest proportion during the end stage. In conclusion, phlegm turbidity and blood stasis were equally serious during the stable stage, and a pathological mechanism caused by blood stasis and toxin existed during the unstable stage. The overall Qi deficiency worsened after PCI, and the end stage was accompanied by the Yin and Yang damage and the aggravation of water retention. There were significant differences in the distribution of clinical characteristics and syndrome elements at different stages of CHD. The pathological process of CHD witnessed the growth and decline of deficiency and excess and the combination of phlegm turbidity and blood stasis, which constituted the basic pathogenesis.

Impact of the uniaxial strain on terahertz modulation characteristics in flexible epitaxial VO2 film across the phase transition.

Exploring flexible electronics is on the verge of innovative breakthroughs in terahertz (THz) communication technology. Vanadium dioxide (VO2) with insulator-metal transition (IMT) has excellent application potential in various THz smart devices, but the associated THz modulation properties in the flexible state have rarely been reported. Herein, we deposited an epitaxial VO2 film on a flexible mica substrate via pulsed-laser deposition and investigated its THz modulation properties under different uniaxial strains across the phase transition. It was observed that the THz modulation depth increases under compressive strain and decreases under tensile strain. Moreover, the phase-transition threshold depends on the uniaxial strain. Particularly, the rate of the phase transition temperature depends on the uniaxial strain and reaches approximately 6 °C/% in the temperature-induced phase transition. The optical trigger threshold in laser-induced phase transition decreased by 38.9% under compressive strain but increased by 36.7% under tensile strain, compared to the initial state without uniaxial strain. These findings demonstrate the uniaxial strain-induced low-power triggered THz modulation and provide new insights for applying phase transition oxide films in THz flexible electronics.

Comparison and Correlation of Corynespora cassiicola Populations from Kiwifruit and Other Hosts Based on Morphology, Phylogeny, and Pathogenicity.

Corynespora leaf spot, which is caused by Corynespora cassiicola (Berk. & M. A. Curtis) C.T. Wei (C. cassiicola), has been globally reported in many plant species. 'Hongyang' was reported as highly sensitive kiwifruit cultivar to C. cassiicola. This cultivar is an important germplasm resource in the Actinidiaceae family and is widely cultivated throughout China. Even though C. cassiicola has been identified as the pathogen associated with kiwifruits in China, the C. cassiicola population from kiwifruit has not been characterized based on morphology, phylogeny, and pathogenicity. In this study, 133 and 48 representative C. cassiicola isolates from kiwifruit and 11 other hosts, respectively, recovered from symptomatic leaves were classified into eight morphological subgroups based on host origins. Using three loci (rDNA ITS, caa5, and act1), a phylogenetic tree showed that C. cassiicola isolates in Sichuan Province were grouped into three clades. All kiwifruit isolates were genetically identical to the rubber isolates from different countries. However, most isolates from other hosts in this study were genetically identical to the cucumber, soybean, and cowpea isolates in China, Brazil, and the United States, and two strawberry isolates clustered with isolates from tomato and other hosts in China, Brazil, and the United States. Furthermore, we confirmed host shift of C. cassiicola among different plant species in this study. Although 51 isolates from kiwifruit and different hosts were pathogenic to kiwifruit, blueberry, cucumber, and soybean, virulence levels of the pathogen were diverse for four hosts. Kiwifruit isolates exhibited host specificity with regards to the original host in degree. In addition, those isolates revealed a correlation between morphology and pathogenicity. The results suggest that C. cassiicola in Sichuan Province were derived from three different phylogenetic lineages. Promotion of the susceptible 'Hongyang' cultivar led to the emergence of a regnant C. cassiicola population from kiwifruit. In conclusion, rapid development of the C. cassiicola-sensitive crop in agricultural systems led to the emergence of a regnant C. cassiicola population. In some dominant populations (e.g., the C. cassiicola population from kiwifruit in this study), host origin was found to be a key factor influencing the morphologic, genetic, and pathogenic characterization of C. cassiicola.

[Research advances in mechanism of lipid infiltration of coronary heart disease and simultaneous treatment of phlegm and blood stasis based on phlegm-blood stasis correlation theory].

Atherosclerosis(AS) is the key pathological basis of coronary heart disease(CHD), and lipid infiltration is a classical theory to explain the pathological mechanism of AS. The theory highlights that the occurrence and development of AS are closely related to abnormal lipid metabolism, with the essence of the pathological reaction caused by the invasion of lipids into arterial intima from plasma. Phlegm and blood stasis are physiologically homologous and subject to pathological co-existence. Phlegm-blood stasis correlation is the basic theory to explain the pathogenesis characteristics of CHD and has important guiding significance for revealing the mecha-nism of lipid infiltration of CHD. Phlegm is the pathological product of abnormal metabolism of Qi, blood, and body fluid, and a gene-ral summary of a series of abnormally expressed lipid substances. Among them, turbid phlegm invades the heart vessels, gradually accumulates, and condenses to achieve the qualitative change from "invisible pathogen" to "tangible pathogen", which corresponds to the mechanism of lipid migration and deposition in the intima of blood vessels, and is the starting factor of the disease. Blood stasis is the continuous development of phlegm, and it is a result of pathological states such as decreased blood fluidity, increased blood coagulation, and abnormal rheology. The fact that blood stasis caused by phlegm accords with the pathological process of "lipid abnormality-circulatory disturbance" and is the central link of the disease. Phlegm and blood stasis aggravate each other and lead to indissoluble cementation. The phlegm-blood stasis combination serves as common pathogen to trigger the disease, which is the inevitable outcome of the disease. Based on the phlegm-blood stasis correlation theory, the simultaneous treatment of phlegm and blood stasis is established. It is found that this therapy can simultaneously regulate blood lipid, reduce blood viscosity, and improve blood circulation, which can fundamentally cut off the biological material basis of the reciprocal transformation between phlegm and blood stasis, thus exerting a significant curative effect.

[Efficacy and mechanism of Xuefu Zhuyu Decoction on model rats of coronary heart disease with heart blood stasis syndrome based on metabolomics].

This study investigated the effects of Xuefu Zhuyu Decoction on myocardial metabolites in a rat model of coronary heart disease with heart blood stasis syndrome and explored the therapeutic mechanism of blood circulation-promoting and blood stasis-removing therapy. SD rats were randomly divided into a sham operation group, a model group, a Xuefu Zhuyu Decoction group(14.04 g·kg~(-1)), and a trimetazidine group(5.4 mg·kg~(-1)). The sham operation group underwent thread insertion without ligation, while the other groups underwent coronary artery left anterior descending branch ligation to induce a model of coronary heart disease with heart blood stasis syndrome. Three days after modeling, drug intervention was performed, and samples were taken after 14 days of intervention. General conditions were observed, and electrocardiogram and cardiac ultrasound indices were measured. Hematoxylin-eosin(HE) staining and Masson staining were used to observe tissue pathological morphology. The enzyme linked immunosorbent assay(ELISA) was used to measure the levels of triglyceride(TG) and total cholesterol(TC) in the serum. Ultra high performance liquid chromatography-quantitative exactive-mass spectrometry(UHPLC-QE-MS) technology was used to screen differential metabolites in myocardial tissue and conduct metabolic pathway enrichment analysis. The results showed that Xuefu Zhuyu Decoction significantly improved the general condition of the model rats, reduced heart rate and ST segment elevation in the electrocardiogram, increased left ventricular ejection fraction(LVEF) and left ventricular fractional shortening(LVFS), and decreased left ventricular internal diameter in diastole(LVIDd) and left ventricular internal diameter in systole(LVIDs). HE staining and Masson staining showed that Xuefu Zhuyu Decoction effectively alleviated myocardial tissue structural disorders, inflammatory cell infiltration, and collagen fiber deposition in the model rats. ELISA results showed that Xuefu Zhuyu Decoction effectively regulated serum TG and TC levels in the model rats. There were significant differences in the metabolic phenotypes of myocardial samples in each group. Fourteen differential metabolites were identified in the Xuefu Zhuyu Decoction group, involving five metabolic pathways, including arginine and proline metabolism, glycerophospholipid metabolism, aminoacyl-tRNA biosynthesis, ether lipid metabolism, and alanine, aspartate, and glutamate metabolism. Xuefu Zhuyu Decoction improved cardiac function and myocardial structural damage in the rat model of coronary heart disease with heart blood stasis syndrome, and its biological mechanism involved the regulation of lipid metabolism, choline metabolism, amino acid metabolism, energy metabolism, and protein synthesis pathways.

[Syndrome differentiation and treatment of coronary heart disease combined with anxiety and depression from stages of phlegm, blood stasis, and toxic pathogen based on theory of "coexistence of diseases and depression syndromes"].

Depression syndromes(anxiety and depression), as typical psychological disorders, often coexist with and mutually influence coronary heart disease(CHD). They constitute a psycho-cardiology disease involving both the blood vessels of the heart and the spirit of the heart. Based on the theory of "coexistence of diseases and depression syndromes", it was proposed that CHD and depression syndromes coexisted independently and were causally related. The factors of depression syndromes go through the entire course of CHD and have different causal relationships at different stages, leading to a pathogenic process of "depression causing disease" or "disease causing depression". In the chronic latent period, phlegm predominates, with depression leading to the production of phlegm. Phlegm accumulation and Qi stagnation initiate a mutual damage process of psycho-cardiology, marking the onset of the disease. In the pathological development period, blood stasis becomes predominant. Depression leads to blood stasis, which further obstructs Qi circulation, accelerating disease progression. In the acute attack period, toxicity becomes crucial. Depression transforms into toxicity, damaging Qi and blood, disturbing the balance of the mind, and inducing a sudden and severe exacerbation of the disease. Based on this, the approach of treating phlegm and depression together, treating blood stasis and depression together, and treating toxicity and depression together by stages was established. Research has found that this approach can simultaneously improve organic damage and emotional disorders, and also has a regulating effect on micro-level syndrome indicators, achieving harmonization of psycho-cardiology in the treatment.

Changes of gut microbiome composition and metabolites associated with hypertensive heart failure rats.

BACKGROUND: The potential role of the gut microbiome (GM) in heart failure (HF) had recently been revealed. However, the underlying mechanisms of the GM and fecal metabolome in HF have not been characterized. The Dahl salt-sensitive rat model of hypertensive heart failure (H-HF) was used to study the clinical symptoms and characteristics. To elucidate the pathogenesis of HF, we combined 16S rRNA gene sequencing and metabolomics to analyze gut microbial compositions and fecal metabolomic profiles of rats with H-HF. RESULTS: PCoA of beta diversity shown that the gut microbiome composition profiles among the three groups were separated. Gut microbial composition was significantly altered in H-HF rats, the ratio of Firmicutes to Bacteroidetes(F/B) increased and the abundance of Muribaculaceae, Lachnospiraceae, and Lactobacillaceae decreased. Significantly altered levels of 17 genera and 35 metabolites were identified as the potential biomarker of H-HF. Correlation analysis revealed that specific altered genera were strongly correlated with changed fecal metabolites. The reduction in short-chain fatty acids (SCFA)-producing bacteria and trimethylamine N-oxide (TMAO) might be a notable characteristic for H-HF. CONCLUSIONS: This is the first study to characterize the fecal microbiome of hypertensive heart failure by integrating 16S rRNA gene sequencing and LC-MS-based metabolomics approaches. Collectively, the results suggesting changes of gut microbiome composition and metabolites are associated with hypertensive heart failure rats.

[Animal model analysis of rheumatoid arthritis based on clinical characteristics of Chinese and Western medicine].

Rheumatoid arthritis(RA) is an autoimmune disease involving multiple joints bilaterally with symmetrical polyarthritis as the main symptom. The high disability rate of this disease seriously affects the quality of life of patients and even threatens their lives. The establishment of a good animal model is of great significance for the diagnosis and clinical prevention of RA. Based on the clinical characteristics of RA in traditional Chinese and Western medicine, the common animal models of RA were summarized, including drug-induced, gene-related, and syndrome and disease combined models. Joint swelling, pain, redness, nodules, and joint deformity are the main criteria for model evaluation, which have certain differences from the clinical diagnostic criteria of RA. From the perspective of syndrome differentiation, the animal model combining syndrome and disease only simulates the syndrome of traditional Chinese medicine and has no direct causal relationship with the formation of RA. In this paper, we analyzed the advantages and disadvantages of animal models of RA and the coincidence degree of the models with the clinical characteristics and then put forward the corresponding recommendations for the evaluation and improvement of these models, aiming to make the animal models of RA closer to the clinical symptoms and play an important role in the clinical diagnosis and treatment of RA.

The Urodynamics and Survival Outcomes of Different Methods of Dissecting the Inferior Hypogastric Plexus in Laparoscopic Nerve-Sparing Radical Hysterectomy of Type C: A Randomized Controlled Study.

BACKGROUND: Little data exist about the impact of dissection methods on bladder function during nerve-sparing radical hysterectomy (NSRH). This randomized controlled trial compared the urodynamic and survival outcomes of different methods dissecting the inferior hypogastric plexus (IHP) during laparoscopic NSRH. METHODS: Eligible patients presenting with stage IB cervical cancer from 9 May 2013 to 27 October 2015 were randomized at a ratio of 1:1 and subjected to waterjet (study group) or traditional blunt (control group) dissection of the IHP for laparoscopic type C radical hysterectomy. Participants were subjected to urodynamic evaluations before and after NSRH. The primary measurement was the proportion of patients with residual urine (RU) ≤ 100 ml, while secondary measurements included urodynamic parameters, disease-free survival (DFS), and overall survival (OS). RESULTS: In total, 191 women met the inclusion criteria, and 160 patients were included in the final analysis, with 80 randomized to each group. At 14 days after NSRH, the study group had more patients with RU ≤ 100 ml than the control group (82.5% vs. 62.5%, p = 0.005). The study group had similar urodynamic outcomes of preoperative and postoperative tests. Comparison with the study group and preoperative tests revealed the control group had significant bladder function impairment at 4 months after NSRH. After a median follow-up of 33 months, the dissection methods had no significant impact on DFS or OS. CONCLUSIONS: Waterjet dissection of the IHP in laparoscopic NSRH resulted in a more rapid return of normal urodynamics without compromising survival outcome. ClinicalTrials.gov Identifiers NCT03015376 (PUMCH-OBGYN-2013), NCT03291236 (SOCM-1).

Giant dual-mode graphene-based terahertz modulator enabled by Fabry-Perot assisted multiple reflection.

We report a high-performance terahertz (THz) modulator with dual operation mode. For the pulse operation mode, the proposed THz modulator has the advantage of high modulation depth (MD) and can operate in a broadband frequency range. We have experimentally achieved a MD larger than 90% for the fifth-order pulse THz echo at 0.8 THz, and the MD stays larger than 75% in a broadband frequency range larger than 1 THz, whereas, for the coherent operation mode, the Fabry-Perot (F-P) interference effect has been taken into consideration and a MD larger than 75% at 0.76 THz has also been realized.

Neoadjuvant chemotherapy followed by radical hysterectomy for stage IB2-to-IIB cervical cancer: a retrospective cohort study.

INTRODUCTION: This study was to evaluate the surgical and survival effects of neoadjuvant chemotherapy (NAC) followed by radical hysterectomy (RH) for cervical cancer with stages IB2 to IIB of FIGO 2009 staging. METHODS: From February 2, 2001 to November 11, 2015, 428 patients received NAC followed by RH in a tertiary hospital, in which all the major procedures were performed by one surgeon. Surgical and survival outcomes were evaluated between the NAC and primary RH groups. RESULTS: A total of 279 (65.2%) patients received NAC, and the overall clinical and complete pathological response rates were 65.9% and 10.8%, respectively. Compared with primary RH patients, NAC patients had more advanced stages, higher recurrence rate, longer median duration of RH, and more median estimated blood loss. After adjusted with baseline risk factors, no significant differences in progression-free or overall survival were observed between the NAC and primary RH groups. However, the responders to NAC had better survival outcomes. CONCLUSIONS: There were no surgical or survival benefits of NAC for patients with cervical cancer of stages IB2 to IIB except for the responders to NAC.

Correlation between IL-17A expression in nasopharyngeal carcinoma tissues and cells and pathogenesis of NPC in endemic areas.

OBJECTIVE: We investigated the correlation between the expression of IL-17A in nasopharyngeal carcinoma tissues and cells and the occurrence and development of NPC was also investigated. METHODS: Forty-five NPC biopsy specimens from January 2014 to January 2016 were selected. Forty-five NPC tissue specimens and 45 chronic nasopharyngitis tissue samples were detected by immunohistochemistry. Statistical methods were used to analyze the correlation between IL-17A expression and the clinicopathological variables of NPC. The NPC patients were followed up. The levels of IL-17A mRNA in 40 NPC tissue specimens and 45 chronic nasopharyngitis tissue samples were detected by real-time PCR. IL-17A expression in 15 NPC tissue specimens and chronic nasopharyngitis tissue samples was further detected by Western blotting assays. RESULTS: IL-17A expression in NPC tissues was significantly higher than that of chronic nasopharyngitis tissues (P < 0.05). IL-17A was expressed in the nucleus and cytoplasm of both NPC tissues and chronic nasopharyngitis tissues. Stage III + IV NPC, tumor volume ≥ 50 mm, and hepatic envelope invasion and cervical lymph node metastasis were associated with significantly higher IL-17A levels versus stage I + II NPC, tumor size < 50 mm, no membrane invasion and lack of cervical lymph node metastasis (P < 0.05). IL-17A was statistically associated with tissue differentiation, serum EBV-lgA levels, and EBV infection. IL-17A-positive patients had significantly longer median survival versus IL-17A-negative patients (21.0 vs. 13.0 months, log-rank test: P < 0.05). Furthermore, 65% (26/40) of NPC tissue samples had significantly higher IL-17A mRNA levels than chronic nasopharyngitis (P < 0.05). IL-17A expression was significantly higher in NPC ≥ 50 mm, stage III + IV NPC and NPC with cervical lymph node invasion than its corresponding chronic nasopharyngitis tissue. CONCLUSION: IL-17A may be involved in the regulation of various malignant biological behaviors of NPC, which is closely related to the occurrence and development of NPC.

VEGF-A and VEGF-B Coordinate the Arteriogenesis to Repair the Infarcted Heart with Vagus Nerve Stimulation.

BACKGROUND/AIMS: Vagus nerve stimulation (VNS) suppresses arrhythmic activity and minimizes cardiomyocyte injury. However, how VNS affects angiogenesis/arteriogenesis in infarcted hearts, is poorly understood. METHODS: Myocardial infarction (MI) was achieved by ligation of the left anterior descending coronary artery (LAD) in rats. 7 days after LAD, stainless-steel wires were looped around the left and right vagal nerve in the neck for vagus nerve stimulation (VNS). The vagal nerve was stimulated with regular pulses of 0.2ms duration at 20 Hz for 10 seconds every minute for 4 hours, and then ACh levels by ELISA in cardiac tissue and serum were evaluated for its release after VNS. Three and 14 days after VNS, Real-time PCR, immunostaining and western blot were respectively used to determine VEGF-A/B expressions and α-SMA- and CD31-postive vessels in VNS-hearts with pretreatment of α7-nAChR blocker mecamylamine (10 mg/kg, ip) or mACh-R blocker atropine (10 mg/kg, ip) for 1 hour. The coronary function and left ventricular performance were analyzed by Langendorff system and hemodynamic parameters in VNS-hearts with pretreatment of VEGF-A/B-knockdown or VEGFR blocker AMG706. Coronary arterial endothelial cells proliferation, migration and tube formation were evaluated for angiogenesis following the stimulation of VNS in coronary arterial smooth muscle cells (VSMCs). RESULTS: VNS has been shown to stimulate VEGF-A and VEGF-B expressions in coronary arterial smooth muscle cells (VSMCs) and endothelial cells (ECs) with an increase of α-SMA- and CD31-postive vessel number in infarcted hearts. The VNS-induced VEGF-A/B expressions and angiogenesis were abolished by m-AChR inhibitor atropine and α7-nAChR blocker mecamylamine in vivo. Interestingly, knockdown of VEGF-A by shRNA mainly reduced VNS-mediated formation of CD31+ microvessels. In contrast, knockdown of VEGF-B powerfully abrogated VNS-induced formation of α-SMA+ vessels. Consistently, VNS-induced VEGF-A showed a greater effect on EC tube formation as compared to VNS-induced VEGF-B. Moreover, VEGF-A promoted EC proliferation and VSMC migration while VEGF-B induced VSMC proliferation and EC migration in vitro. Mechanistically, vagal neurotransmitter acetylcholine stimulated VEGF-A/B expressions through m/nACh-R/PI3K/Akt/Sp1 pathway in EC. Functionally, VNS improved the coronary function and left ventricular performance. However, blockade of VEGF receptor by antagonist AMG706 or knockdown of VEGF-A or VEGF-B by shRNA significantly diminished the beneficial effects of VNS on ventricular performance. CONCLUSION: VNS promoted angiogenesis/arteriogenesis to repair the infracted heart through the synergistic effects of VEGF-A and VEGF-B.

Giant impact of self-photothermal on light-induced ultrafast insulator-to-metal transition in VO2 nanofilms at terahertz frequency.

Ultrafast detection and switching of light are key processes in high-speed optoelectronic devices. However, the performances of VO2-based optoelectronics are strongly degraded by photothermal. The mechanism of the latter is still unclear. Here, by using femtosecond-laser (fs-laser) driven kinetic terahertz wave absorption, we quantitatively separate slow photothermal response and ultrafast photodoping response (e.g. light-induced insulator-to-metal transition) from second- to picosecond-timescales, and discover the competing interplay between them. With self-photothermal (mainly determined by fs-laser pulse repetition rate and pump fluence), the ultrafast transition time was degraded by 190% from 50 ps to 95 ps, the ultrafast transition threshold was decreased to 82% from 11mJ/cm2 to 9mJ/cm2, while the amplitudes of the two photoresponse are competing. Percolation theory, along with the macroscopic conductivity response, is used to explain the competing interplay. Our findings are relevant for designing and optimizing VO2-based ultrafast optoelectronic devices.

Dual-mode tunable terahertz generation in lithium niobate driven by spatially shaped femtosecond laser.

A new approach for dual-mode (namely broadband mode and narrowband mode) terahertz (THz) pulses generation in a single lithium niobate (LN) crystal excited by spatially shaped tilted-pulse-front femtosecond (fs) laser pulse was proposed and experimentally demonstrated. The two THz emission modes are generated simultaneously while spatially separated. Both central frequency and bandwidth of narrowband THz emission is controllable by in situ tuning the spatial modulation period and beam size of the fs-laser, and the broadband (0.1-1.5 THz) THz emission keeps almost unchanged while tuning the narrowband emission. Further optimization achieves the narrowband THz emission with energy spectral density up to 0.27 µJ/THz and with bandwidth narrowly down to 23 GHz. Such dual-mode THz source is useful for nonlinear THz optics, such as selected resonant THz excitation with broadband THz probe spectroscopy of crystalline matters.

Adoptive Cellular Gene Therapy for the Treatment of Experimental Autoimmune Polychondritis Ear Disease.

In the past, the clinical therapy for autoimmune diseases, such as autoimmune polychondritis ear disease, was mostly limited to nonspecific immunosuppressive agents, which could lead to variable responses. Currently, gene therapy aims at achieving higher specificity and less adverse effects. This concept utilizes the adoptive transfer of autologous T cells that have been retrovirally transduced ex vivo to express and deliver immunoregulatory gene products to sites of autoimmune inflammation. In the animal model of collagen-induced autoimmune polychondritis ear disease (CIAPED), the adoptive transfer of IL-12p40-expressing collagen type II (CII)-specific CD4+ T-cell hybridomas resulted in a significantly lower disease incidence and severity compared with untreated or vector-only-treated animals. In vivo cell detection using bioluminescent labels showed that transferred CII-reactive T-cell hybridomas accumulated in the inflamed earlobes of the mice with CIAPED. In vitro analysis demonstrated that IL-12p40-transduced T cells did not affect antigen-specific T-cell activation or systemic anti-CII Ab responses. However, IL-12p40-transduced T cells suppressed IFN-γ and augmented IL-4 production, indicating their potential to act therapeutically by interrupting Th1-mediated inflammatory responses via augmenting Th2 responses. These results indicate that the local delivery of IL-12p40 by T cells could inhibit CIAPED by suppressing autoimmune responses at the site of inflammation.

Generation of 0.19-mJ THz pulses in LiNbO3 driven by 800-nm femtosecond laser.

A cylindrical lens telescope tilted-pulse-front pumping scheme was proposed for high energy terahertz (THz) pulse generation. This scheme allows higher pump energy to be used with lower saturation effects under high pump fluence, and higher THz generation efficiency was achieved within large range of pump energy. The optimum pump pulse duration and crystal cooling temperature for THz generation in LiNbO3 (LN) crystal were also researched systematically. Excited by 800-nm laser, up to 0.19 mJ THz pulse energy and 0.27% conversion efficiency was demonstrated under 800-nm 400-fs laser excitation with ~100-mJ pulse energy and 150-K LN cooling temperature.

Asthma control and severe exacerbations in patients with moderate or severe asthma in Jilin Province, China: a multicenter cross-sectional survey.

BACKGROUND: No systemic evaluation of asthma control in Jilin Province has been reported. Asthma control might provide the basis for asthma management in this region. A multicenter hospital-based cross-sectional study was performed to investigate the asthma control and related factors for severe asthma exacerbations in patients with moderate or severe asthma in Jilin Province, China. METHODS: The study enrolled 1546 patients in five grade one general hospitals from January to December 2013. Asthma medication, patient self-management, asthma control test (ACT) scores and frequency of severe asthma exacerbations during the follow-up (12 months) were collected via a follow-up questionnaire. RESULTS: In the study, 889 patients provided a complete follow-up questionnaire. Severe asthma exacerbations occurred in 54.89 % of patients. ACT score ≤15, asthma medication ≤ 3 months, severe asthma, income level lower than average Per Capita Disposable Income (PCDI) and a lower educational level were risk factors of a severe exacerbation. CONCLUSIONS: Poor adherence to asthma medication, poor asthma symptom control, lower income, a low educational level might be possible reasons for the high incidence of severe asthma exacerbations and poor asthma control in Jilin Province of China.