Laser-Induced Inelastic Diffraction from Strong-Field Double Ionization.

In this Letter, we propose a novel laser-induced inelastic diffraction (LIID) scheme based on the intense-field-driven atomic nonsequential double ionization (NSDI) process and demonstrate that, with this LIID approach, the doubly differential cross sections (DDCSs) of the target ions, e.g., Ar^{+} and Xe^{+}, can be accurately extracted from the two-dimensional photoelectron momentum distributions in the NSDI process of the corresponding atoms. The extracted DDCSs exhibit a strong dependence on both the target and the laser intensity, in good agreement with calculated DDCSs from the scattering of free electrons. The LIID scheme may be extended to molecular systems and provides a promising approach for imaging of the gas-phase molecular dynamics induced by a strong laser field with unprecedented spatial and temporal resolution.

Laser intensity determination using nonadiabatic tunneling ionization of atoms in close-to-circularly polarized laser fields.

We conceive an improved procedure to determine the laser intensity with the momentum distributions from nonadiabatic tunneling ionization of atoms in the close-to-circularly polarized laser fields. The measurements for several noble gas atoms are in accordance with the semiclassical calculations, where the nonadiabatic effect and the influence of Coulomb potential are included. Furthermore, the high-order above-threshold ionization spectrum in linearly polarized laser fields for Ar is measured and compared with the numerical calculation of the time-dependent Schrödinger equation in the single-active-electron approximation to test the accuracy of the calibrated laser intensity.

Elliptical polarization favors long quantum orbits in high-order above-threshold ionization of noble gases.

We demonstrate the significant role of long quantum orbits in strong-field atomic processes by investigating experimentally and theoretically the above-threshold ionization spectra of noble gases in intense elliptically polarized laser pulses. With increasing laser ellipticity, the yields of different energy regions of the measured electron spectrum in high-order above-threshold ionization drop at different rates. The experimental features can be reproduced by a theoretical simulation based on quantum-orbit theory, revealing that increasing ellipticity favors the contributions of the long quantum orbits in the high-order above-threshold ionization process.

Silencing LCN2 suppresses oral squamous cell carcinoma progression by reducing EGFR signal activation and recycling.

BACKGROUND: EGFR is an important signal involved in tumor growth that can induce tumor metastasis and drug resistance. Exploring targets for effective EGFR regulation is an important topic in current research and drug development. Inhibiting EGFR can effectively inhibit the progression and lymph node metastasis of oral squamous cell carcinoma (OSCC) because OSCC is a type of cancer with high EGFR expression. However, the problem of EGFR drug resistance is particularly prominent, and identifying a new target for EGFR regulation could reveal an effective strategy. METHODS: We sequenced wild type or EGFR-resistant OSCC cells and samples from OSCC patients with or without lymph node metastasis to find new targets for EGFR regulation to effectively replace the strategy of directly inhibiting EGFR and exert an antitumor effect. We then investigated the effect of LCN2 on OSCC biological abilities in vitro and in vivo through protein expression regulation. Subsequently, we elucidated the regulatory mechanism of LCN2 through mass spectrometry, protein interaction, immunoblotting, and immunofluorescence analyses. As a proof of concept, a reduction-responsive nanoparticle (NP) platform was engineered for effective LCN2 siRNA (siLCN2) delivery, and a tongue orthotopic xenograft model as well as an EGFR-positive patient-derived xenograft (PDX) model were applied to investigate the curative effect of siLCN2. RESULTS: We identified lipocalin-2 (LCN2), which is upregulated in OSCC metastasis and EGFR resistance. Inhibition of LCN2 expression can effectively inhibit the proliferation and metastasis of OSCC in vitro and in vivo by inhibiting EGFR phosphorylation and downstream signal activation. Mechanistically, LCN2 binds EGFR and enhances the recycling of EGFR, thereby activating the EGFR-MEK-ERK cascade. Inhibition of LCN2 effectively inhibited the activation of EGFR. We translated this finding by systemic delivery of siLCN2 by NPs, which effectively downregulated LCN2 in the tumor tissues, thereby leading to a significant inhibition of the growth and metastasis of xenografts. CONCLUSIONS: This research indicated that targeting LCN2 could be a promising strategy for the treatment of OSCC.

[Early treatment of atelectasis by bronchoscopy in craniotomy patients].

OBJECTIVE: To investigate the safety and effects of early bronchoscopy on atelectasis of the ventilation patients, whom had experienced craniotomy for severe cranial trauma and hemorrhage. METHODS: Fifty-five patients suffered from severe cranial trauma and hemorrhage with Glascow coma scores (GCS) less than 8 complicated by atelectasis after craniotomy were early given sputum suction by bronchoscope via extratracheal intubation and broncho-alveolar lavage (BAL) during tracheal intubation and mechanical ventilation. During the treatment, patients' consciousness, vital signs and arterial blood gas were closely monitored. The relevant data, before, during (5, 10, and 25 minutes), bronchoscopy treatment completed and 30 minutes after bronchoscopy, were recorded and analyzed. RESULTS: Eighty-two time of bronchoscopies and 111 time of local BALs in 55 patients were completed and were effective for atelectasis. The patient's GCS (5.6±2.5 vs. 5.4±2.6, P>0.05), heart rate (HR), respiratory rate (RR), systolic blood pressure (SBP), blood oxygenous saturation (SaO(2)) were not deteriorated during bronchoscopy. Compared with pre-bronchoscopy, the HR and SBP decreased (HR: 88.2±14.2 bpm vs. 98.2±18.3 bpm, SBP: 110.6±18.2 mm Hg vs. 118.4±18.5 mm Hg, both P<0.05), and SaO(2) increased (0.982±0.022 vs. 0.945±0.035, P<0.05), pH, arterial partial pressure of oxygen (PaO(2)) and arterial partial pressure of carbon dioxide (PaCO(2)) had no significant changes during bronchoscopy. There was obviously increased in PaO(2) (84.5±14.4 mm Hg, 81.6±18.2 mm Hg vs. 76.2±15.4 mm Hg, both P<0.05), and decreased in PaCO(2) (27.0±12.8 mm Hg, 29.3±18.2 mm Hg vs. 36.5±11.6 mm Hg, both P<0.05) respectively, significantly decreased in alveolar arterial pressure of oxygen difference [P ((A-a))O(2)] at 10 minutes and 25 minutes, and at the time bronchoscopy treatment completed and the time 30 minutes after compared with before bronchoscopy (36.1±4.7 mm Hg, 32.4±6.2 mm Hg, 32.5±5.2 mm Hg, 31.2±7.2 mm Hg vs. 38.5±5.6 mm Hg, all P<0.05). All patients had not encounter side effects related with bronchoscopy and ventilation. CONCLUSION: The bronchoscope via extratracheal intubation for sputum suction and BAL were safe and effective treatment to the patients suffered from severe cranial trauma or hemorrhage complicated by atelectasis after craniotomy during mechanical ventilation, without obvious changes of the vital signs.

RPS3 Promotes the Metastasis and Cisplatin Resistance of Adenoid Cystic Carcinoma.

Background: Adenoid cystic carcinoma (ACC) is a malignant tumor in salivary gland tissue, that is characterized by strong invasiveness and lung metastasis, leading to poor survival rates. RPS3 is been reported to be associated with the biological functions of tumor cells. This study explored the regulatory effect of RPS3 in ACC to provide new therapeutic targets for ACC therapy. Methods: We reviewed the clinical and pathologic data of 73 ACC patients. The expression of RPS3 was examined in ACC by immunohistochemistry. Transwell, wound healing, half-maximal inhibitory concentration (IC50) and other experiments were used to determine the regulatory effect of RPS3 on ACC functions. Coimmunoprecipitation and mass spectrometry analysis were used to detect the binding proteins of RPS3, mechanisms by which RPS3/STAT1/NF-kB signaling regulates ACC behavior were assessed using western blotting (WB), qPCR, etc. To explore the regulatory effect of RPS3 on ACC in vivo, we constructed nude mouse sciatic nerve infiltration model and a lung metastasis model for studies. Results: High RPS3 expression was associated with metastasis and a poor prognosis in ACC patients. Inhibition of RPS3 expression reduced ACC migration, invasion and cisplatin resistance, and overexpression of RPS3 promoted ACC migration, invasion and cisplatin resistance. Further experiments revealed that RPS3 can activate the STAT1/NF-kB signaling pathway and regulate ACC behavior through binding to STAT1. The incidence of sciatic nerve infiltration and lung metastasis in nude mice after RPS3 knockdown was lower than that of the control group in vivo. Conclusion: RPS3 is highly expressed and associated with the prognosis and survival of ACC patients. The RPS3/STAT1/NF-kB pathway may play an important regulatory role in ACC migration, invasion and chemoresistance. As a new therapeutic target of ACC, its clinical application value is worthy of attention and further exploration.

HPV Enhances HNSCC Chemosensitization by Inhibiting SERPINB3 Expression to Disrupt the Fanconi Anemia Pathway.

Head and neck squamous cell carcinoma (HNSCC) is the most common malignant tumor of the head and neck, and the prognosis of patients is poor due to chemotherapeutic resistance. Interestingly, patients with HNSCC induced by human papillomavirus (HPV) infection are more sensitive to chemotherapy and display a better prognosis than HPV-negative patients. The biological relevance of HPV infection and the mechanism underlying chemosensitivity to cisplatin remain unknown. Herein, SERPINB3 is identified as an important target for regulation of cisplatin sensitivity by HPV-E6/E7 in HNSCC. Downregulation of SERPINB3 inhibits cisplatin-induced DNA damage repair and enhances the cytotoxicity of cisplatin. In detail, decreasing SERPINB3 expression reduces the USP1-mediated deubiquitination of FANCD2-FANCI in the Fanconi anemia pathway, thereby interfering with cisplatin-induced DNA interstrand crosslinks repair and further contributing to HNSCC cell apoptosis. To translate this finding, pH-responsive nanoparticles are used to deliver SERPINB3 small interfering RNA in combination with cisplatin, and this treatment successfully reverses cisplatin chemotherapeutic resistance in a patient-derived xenograft model from HPV-negative HNSCC. Taken together, these findings suggest that targeting SERPINB3 based on HPV-positive HNSCC is a potential strategy to overcome cisplatin resistance in HPV-negative HNSCC and improves the prognosis of this disease.

GSDMD enhances cisplatin-induced apoptosis by promoting the phosphorylation of eIF2α and activating the ER-stress response.

GSDMD is the key effector of pyroptosis, but its non-pyroptosis-related functions have seldom been reported. Here, we report that GSDMD is overexpressed in different types of tumours, including head and neck squamous-cell carcinoma, and it promotes the sensitivity of tumour cells to cisplatin. Unexpectedly, the enhanced cisplatin sensitivity is mediated by apoptosis but not pyroptosis, the well-known function of GSDMD. Furthermore, we found that GSDMD can activate the unfolded protein response by promoting the phosphorylation of eIF2α. Mechanistically, we demonstrated that GSDMD can directly bind to eIF2α and enhance the interaction between eIF2α and its upstream kinase PERK, leading to eIF2α phosphorylation. Consequently, the protein levels of ATF-4 were upregulated, downstream apoptosis-related proteins such as CHOP were activated, and apoptosis was induced. Remarkably, activation of endoplasmic-reticulum (ER) stress induced by GSDMD promotes cell apoptosis during cisplatin chemotherapy, thereby increasing the treatment sensitivity of tumours. Therefore, for the first time, our work reveals an unreported nonpyroptotic function of the classic pyroptosis protein GSDMD: it promotes cell apoptosis during cisplatin chemotherapy by inducing eIF2α phosphorylation and ER stress, which are related to the drug sensitivity of tumours. Our study also indicated that GSDMD might serve as a biomarker for cisplatin sensitivity.

Porphyromonas gingivalis induced inflammatory responses and promoted apoptosis in lung epithelial cells infected with H1N1 via the Bcl­2/Bax/Caspase­3 signaling pathway.

The aim of the present study was to investigate the effects of Porphyromonas gingivalis (P. gingivalis) on inflammatory cytokine and nitic oxide (NO) production in lung epithelial cells infected with H1N1, and the underlying mechanisms. Lung epithelial cells were co­infected with P. gingivalis and H1N1. The concentrations of tumor necrosis factor­α (TNF­α), interleukin (IL)­1ß and IL­6 were detected via an ELISA, and the concentration of NO was detected by the nitrate reductive enzymatic method at 4, 8, 12 and 24 h following infection. The expression levels of inducible NO synthase (iNOS) was detected by western blotting. The apoptotic rate of lung epithelial cells was detected by flow cytometry. The relative protein expression levels of B­cell lymphoma­2 (Bcl­2), Bcl­2­associated X protein (Bax) and caspase­3 in lung epithelial cells were detected by western blotting. Compared with the control group, the concentration of the inflammatory cytokines TNF­α, IL­1ß and IL­6 exhibited a significant increase (P<0.05) in the viral­infected, bacterial­infected and co­infected groups. The concentration of NO also increased significantly (P<0.05), along with the rise in the expression levels of iNOS (P<0.05) and the increase in the apoptosis rate of lung epithelial cells (P<0.05). The relative expression levels of caspase­3 and Bax proteins were increased significantly in the viral­ and bacterial­infected groups when compared with the control. The relative expression levels of Bcl­2 protein exhibited a significant decrease in lung epithelial cells following the co­infection with P. gingivalis and H1N1 compared with the control (P<0.05). The results of the present study revealed that the combination of P. gingivalis and H1N1 infection in lung epithelial cells may promote the production of inflammatory cytokines and increase NO production, leading to increased levels of apoptosis in lung epithelial cells via the Bcl­2/Bax/caspase­3 signaling pathway.

Carbon dioxide laser treatment of facial papilloma in children: case report and literature review / 口腔疾病防治

Objective@#To investigate the feasibility of using a carbon dioxide(CO2) laser in the treatment of facial papilloma in children and to evaluate its curative effect and prognosis.@*Methods @#A case of pediatric facial papilloma treated with a CO2 laser was reported, and the effects of this disease and CO2 laser treatment were reviewed and analyzed in combination with the literature. @* Results@#Under general anesthesia, the lesion tissue of the left lip was excised for pathological biopsy, and the diagnosis was maxillofacial papilloma. The lesions were surgically ablated in stages with a CO2 laser, and erythromycin ointment was applied to the surgical incision after surgery. A total of three rounds of CO2 laser treatment were performed for 3 treatment courses. The child had no complications during or after the operation, the facial appearance was significantly improved, and there was no sign of recurrence during the 6-month follow-up. A literature review showed that CO2 lasers have been widely used in the excision of various surface lesions. In clinical practice, continuous CO2 laser with power of 10-50 W and wavelength of 10.6 μm is used to treat superficial tissue lesions, which can achieve accurate vaporization resection of diseased tissue, less bleeding and a good prognosis.@* Conclusion@#CO2 laser was accurate and minimally invasive for the removal of facial papilloma in children.

Research progress on HPV-positive oropharyngeal carcinoma sensitive to radiation therapy / 口腔疾病防治

@#Oropharyngeal carcinoma is a highly heterogeneous disease that is mainly caused by tobacco and alcohol abuse or high-risk human papillomavirus (HPV) infection. HPV-positive oropharyngeal carcinoma and HPV-negative oropharyngeal carcinoma have obvious differences in etiology, epidemiology and prognosis; therefore, different methods should be adopted for treatment. It is known that the TP53 gene is not mutated in HPV-positive oropharyngeal carcinoma, and radiation therapy can activate it and induce cell apoptosis via DNA damage. There are common repair pathways to DNA damage, such as nonhomologous end joining, and this pathway is more sensitive to radiotherapy under the inhibition of HPV oncoprotein. In addition, the further activation of the immune response under the effect of radiation also participates in the elimination of tumors. In this paper, we reviewed the research on the sensitivity of HPV-positive oropharyngeal cancer to radiotherapy to provide a scientific basis for targeted treatment for various pathogenic factors and clinical stages of oropharyngeal cancer in the future.

Long-Range Coulomb Effect in Intense Laser-Driven Photoelectron Dynamics.

In strong field atomic physics community, long-range Coulomb interaction has for a long time been overlooked and its significant role in intense laser-driven photoelectron dynamics eluded experimental observations. Here we report an experimental investigation of the effect of long-range Coulomb potential on the dynamics of near-zero-momentum photoelectrons produced in photo-ionization process of noble gas atoms in intense midinfrared laser pulses. By exploring the dependence of photoelectron distributions near zero momentum on laser intensity and wavelength, we unambiguously demonstrate that the long-range tail of the Coulomb potential (i.e., up to several hundreds atomic units) plays an important role in determining the photoelectron dynamics after the pulse ends.

Application of fiberoptic bronchscopy in patients with acute exacerbations of chronic obstructive pulmonary disease during sequential weaning of invasive-noninvasive mechanical ventilation.

BACKGROUND: Early withdrawal of invasive mechanical ventilation (IMV) followed by noninvasive MV (NIMV) is a new strategy for changing modes of treatment in patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD) with acute respiratory failure (ARF). Using pulmonary infection control window (PIC window) as the switch point for transferring from invasive to noninvasive MV, the time for early extubation can be more accurately judged, and therapy efficacy can be improved. This study aimed to prospectively investigate the clinical effectiveness of fiberoptic bronchscopy (FOB) in patients with AECOPD during sequential weaning of invasive-noninvasive MV. METHODS: Since July 2006 to January 2011, 106 AECOPD patients with ARF were treated with comprehensive medication and IMV after hospitalization. Patients were randomly divided into two groups according to whether fiberoptic bronchoscope is used (group A, n=54) or not (group B, n=52) during sequential weaning from invasive to noninvasive MV. In group A, for sputum suction and bronchoalveolar lavage (BAL), a fiberoptic bronchoscope was put into the airway from the outside of an endotracheal tube, which was accompanied with uninterrupted use of a ventilator. After achieving PIC window, patients of both groups changed to NIMV mode, and weaned from ventilation. The following listed indices were used to compare between the groups after treatment: 1) the occurrence time of PIC, the duration of MV, the length of ICU stay, the success rate of weaning from MV for the first time, the rate of reventilation and the occurrence rate of ventilator-associated pneumonia (VAP); 2) the convenience and safety of FOB manipulation. The results were compared using Student's t test and the Chi-square test. RESULTS: The occurrence time of PIC was (5.01±1.49) d, (5.87±1.87) d in groups A and B, respectively (P<0.05); the duration of MV was (6.98±1.84) d, (8.69±2.41) d in groups A and B, respectively (P<0.01); the length of ICU stay was (9.25±1.84) d, (11.10±2.63) d in groups A and B, respectively (P<0.01); the success rate of weaning for the first time was 96.30%, 76.92% in groups A and B, respectively (P<0.01); the rate of reventilation was 5.56%, 19.23% in groups A and B, respectively (P<0.05); and the occurrence rate of VAP was 3.70%, 23.07% in groups A and B, respectively (P<0.01). Moreover, it was easy and safe to manipulate FOB, and no side effect was observed. CONCLUSIONS: The application of FOB in patients with AECOPD during sequential weaning of invasive-noninvasive MV is effective in ICU. It can decrease the duration of MV and the length of ICU stay, increase the success rate from weaning MV for the first time, reduce the rate of reventilation and the occurrence rate of VAP. In addition, such a method is convenient and safe in patients of this kind.