[Establishment and validation of nomogram prediction model for complicated acute appendicitis].

Objective: To establish and internally validate a nomogram model for predicting complicated acute appendicitis (CA). Methods: The clinical data from 663 acute appendicitis patients from the First Affiliated Hospital of Anhui University of Traditional Chinese Medicine from October 2015 to October 2022 were retrospectively analyzed. There were 411 males and 252 females, aged (M (IQR)) 41 (22) years (range: 18 to 84 years). There were 516 cases of CA and 147 cases of uncomplicated acute appendicitis. The minimum absolute contraction and selection operator regression model was used to screen the potential relative factors of CA, and the screened factors were included in the Logistic regression model for multivariate analysis. Software R was used to establish a preoperative CA nomogram prediction model, the receiver operating characteristic curve of the model was drawn, and the value of area under the curve (AUC) was compared to evaluate its identification ability, and the Bootstrap method was used for internal verification. Results: The elderly (age≥60 years) (OR=2.428, 95%CI: 1.295 to 4.549), abdominal pain time (every rise of 1 hour) (OR=1.089, 95%CI: 1.072 to 1.107), high fever (body temperature≥39 ℃) (OR=1.122, 95%CI: 1.078 to 1.168), total bilirubin (every rise of 1 µmol/L) (OR=2.629, 95%CI: 1.227 to 5.635) were independent relative factors of CA (all P<0.05). The AUC of this model was 0.935 (95%CI: 0.915 to 0.956). After internal verification using the Bootstrap method, the model still had a high discrimination ability (AUC=0.933), and the predicted CA curve was still in good agreement with the actual clinical CA curve. Conclusion: The clinical prediction model based on the elderly (age≥60 years), prolonged abdominal pain time, high fever (body temperature≥39 ℃), and increased total bilirubin can help clinicians effectively identify CA.

Two Schiff base iodide compounds as iodide ion conductors showing high conductivity.

Here, we reported the crystal structures, dielectric and conducting properties of two Schiff base iodide compounds [m-BrBz-1-APy]I3 (1) and [o-FBz-1-APy]I3 (2). The Schiff base cations build irregular channel frameworks, and the polyiodide anions are located in the channel. The impedance spectra demonstrated that the two compounds show intrinsic iodide ion conductance with higher conductivity of 1.03(4) × 10-4 S cm-1 at 343 K for 1 and 4.94(3) × 10-3 S cm-1 at 353 K for 2. The dielectric modulus analysis further confirmed that the conductance contributed to the migration of iodide ions.

Methotrexate/mifepristone-combined with embryo removal in the treatment of caesarean scar pregnancy.

OBJECTIVE: The aim of this study was to compare the effect of different administration modalities of methotrexate (MTX)/mifepristone in the initial medication stage, followed by embryo transfer in the treatment of caesarean scar pregnancy (CSP). PATIENTS AND METHODS: A retrospective analysis of 66 CSP patients who received treatment in our hospital from January 2015 to July 2021 was performed, and participants were divided into three groups: Group one (n=14) received mifepristone followed by embryo removal treatment, Group two (n=29) received MTX followed by embryo removal, and Group three (n=23) received a methotrexate/mifepristone combined treatment followed by embryo removal. The basic findings were analysed, along with the curative effects between the three groups. Risk factors predicting additional treatment after initial intervention failure were analysed. RESULTS: There were statistically significant differences in gestational age, hospitalization days, costs, myometrial thickness, cardiac activity, and mean sac diameter between groups (p<0.05) after grouping by eight weeks. The initial intervention success rates were 92.86%, 89.66%, and 65.22% in Group one, two, and three, respectively (p<0.05), while the complication rates were 14.29%, 6.90%, and 26.87%, respectively (p>0.05). After grouping according to eight weeks of gestational age, the difference in initial serum ß-hCG between Group two and three was statistically significant (p<0.05). Mean sac diameter was a risk factor for additional treatment after initial intervention failure, with an odds ratio of 1.113 (p<0.05). A cut-off of 22.75 mm was a preferable indicator. CONCLUSIONS: MTX/mifepristone followed by embryo removal is a reliable way to treat CSP. Mean sac diameter was a risk factor for additional treatment after initial intervention failure.

[Significance of early lymphocyte-platelets ratio on the prognosis of patients with extensive burns].

Objective: To analyze the changing trend and characteristics of lymphocyte-platelets ratio (LPR) of early stage in patients with extensive burns, and to explore the prognostic significance of LPR. Methods: A retrospective case series study was conducted. From January 2008 to December 2018, 244 patients with extensive burns were admitted to the First Affiliated Hospital of Naval Medical University, including 181 males and 63 females, aged (44±16) years. The total burned area of patients was 60.0% (42.0%, 85.0%) total body surface area. Platelet and lymphocyte test results of patients were collected on the 1st, 2nd and 3rd day after admission, and LPR of patients was calculated to analyze the changing trend of the three days after admission. Univariate and multivariate logistic regression analysis were conducted to investigate the risk factors or independent risk factors for death of patients, including age, sex, total burn area, area of full-thickness burns and above, inhalation injury, and LPR. According to the 1st day's LPR after admission of patients, the receiver operating characteristic (ROC) curve predicting death of patients was drawn to find the optimal value of LPR. Patients were divided into high LPR group (n=136) and low LPR group (n=108) based on the optimal value of LPR, and the clinical data of total burn area, area of full-thickness burns and above, inhalation injury, tracheotomy, offline time of patients within 28 days, and mortality in the 2 groups were compared. The surviving curve of patients was drawn by Kaplan-Meier method to predict the difference of the 90-day survival rate between the two groups of patients. Data were statistically analyzed with Student's t test, Mann-Whitney U test, and chi-square test. Results: Within 3 days of admission, the LPR of patients showed a time-dependent upward trend. LPR of patients on the 2nd and 3rd day after admission was 8.6 (5.3, 14.4) and 8.6 (4.9, 13.7), respectively, which were significantly higher than the 1st day's 6.3 (4.2, 9.8), with Z values of -4.25 and -3.43, respectively, P<0.01. Univariate logistic regression analysis showed that age, total burn area, area of full-thickness burns and above, inhalation injury, and LPR were all risk factors for death of patients (with odds ratios of 1.03, 1.73, 1.31, 4.74, and 3.11, respectively, 95% confidence intervals of 1.01-1.06, 1.40-2.13, 1.21-1.42, 1.62-13.86, and 1.41-6.88, respectively, P<0.01). Multivariate logistic regression analysis showed that age, area of full-thickness burns and above, and LPR were independent risk factors for death of patients (with odds ratios of 1.06, 1.36, and 2.85, respectively, 95% confidence intervals of 1.03-1.09, 1.19-1.55, 1.02-7.97, P<0.05 or P<0.01). The area under ROC curve of the 1st day's LPR, predicting death of patients, was 0.61 (with 95% confidence interval of 0.51-0.71, P<0.05), and the optimal predicted value was 5.8 with corresponding sensitivity of 77% and specificity of 52% respectively. The total burn area, area of full-thickness burns and above, rates of incidence of inhalation injury, tracheotomy, and mortality of patients in high LPR group were significantly higher than those in low LPR group (with Z values of -3.06 and -3.19, χ2 values of 5.42, 11.64, and 8.45, respectively, P<0.05 or P<0.01). The offline time of patients within 28 days in high LPR group was significantly shorter than that in low LPR group (Z=-2.98, P<0.01). Kaplan-Meier survival analysis showed that the 90-day survival rate of admission of patients in low LPR group was significantly higher than that of patients in high LPR group (χ2=8.24, P<0.01). Conclusions: The early LPR of patients with extensive burns showed a time-dependent upward trend. The LPR on the first day after admission that is closely correlated with total burn area, area of full-thickness and deeper burns, inhalation injury, tracheotomy, and mortality of patients, is an independent risk factor for the prognosis of patients with extensive burns. The first day's LPR after admission is significantly correlated with the 90-day survival rate of patients, which can be used as an evaluation index for the severity of extensive burns.

Multifunctional Chiral Three-Dimensional Phosphite Frameworks Showing Dielectric Anomaly and High Proton Conductivity.

Chair 3D Co(II) phosphite frameworks have been prepared by the ionothermal method. It belongs to chiral space group P3221, and the whole framework can be topologically represented as a chiral 4-connected qtz net. It shows a multistep dielectric response arising from the reorientation of Me2-DABCO in the chiral cavities. It can also serve as a pron conductor with high conductivity, 1.71 × 10-3 S cm-1, at room temperature, which is attributed to the formation of denser hydrogen-bonding networks providing efficient proton-transfer pathways.

Copper Centers in the Cryo-EM Structure of Particulate Methane Monooxygenase Reveal the Catalytic Machinery of Methane Oxidation.

The particulate methane monooxygenase (pMMO) is the first enzyme in the C1 metabolic pathway in methanotrophic bacteria. As this enzyme converts methane into methanol efficiently near room temperature, it has become the paradigm for developing an understanding of this difficult C1 chemistry. pMMO is a membrane-bound protein with three subunits (PmoB, PmoA, and PmoC) and 12-14 coppers distributed among different sites. X-ray crystal structures that have revealed only three mononuclear coppers at three sites have neither disclosed the location of the active site nor the catalytic mechanism of the enzyme. Here we report a cyro-EM structure of holo-pMMO from Methylococcus capsulatus (Bath) at 2.5 Å, and develop quantitative electrostatic-potential profiling to scrutinize the nonprotein densities for signatures of the copper cofactors. Our results confirm a mononuclear CuI at the A site, resolve two CuIs at the B site, and uncover additional CuI clusters at the PmoA/PmoC interface within the membrane (D site) and in the water-exposed C-terminal subdomain of the PmoB (E clusters). These findings complete the minimal set of copper factors required for catalytic turnover of pMMO, offering a glimpse of the catalytic machinery for methane oxidation according to the chemical principles underlying the mechanism proposed earlier.

Effects of miR-32 targeting PTEN on proliferation and apoptosis of myeloma cells.

OBJECTIVE: To explore the effects of micro ribonucleic acid (miR)-32 on the proliferation and apoptosis of myeloma cells, and to verify whether it exerts its function by targeting phosphatase and tensin homolog deleted on chromosome ten (PTEN). PATIENTS AND METHODS: The differentially expressed miRNAs were screened in healthy people and myeloma patients. The myeloma U266 cells transfected with negative control (NC) were used as control group, those transfected with miR-32 inhibitor as transfection group, and those transfected with miR-32 inhibitor and treated with PTEN inhibitor SF1670 as the transfection + inhibitor group. Then, the cell proliferation and apoptosis in each group were detected using the 5-Ethynyl-2'-deoxyuridine (EdU) kit and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay, respectively. Finally, the expressions of apoptosis-related proteins B-cell lymphoma-2 (Bcl-2), Bcl-2 homologous antagonist/killer (Bak), caspase-9, and survivin were detected. RESULTS: The expressions of some miRNAs and genes in myeloma patients were significantly different from those in healthy people. In myeloma patients, miR-32, miR-126, miR-123, and miR-183 were significantly highly expressed, while miR-5, miR-76, and miR-50 were remarkably lowly expressed. After myeloma U266 cells were transfected with the miR-32 inhibitor, the expression of miR-32 markedly declined. In addition, the mRNA expression of PTEN in myeloma cells rose after transfection with the miR-32 inhibitor, and declined after addition of the PTEN inhibitor SF1670, which were consistent with the results of Western blotting. Besides, the proliferation ability of myeloma cells was evidently weakened after transfection with the miR-32 inhibitor, while it was restored to a certain extent after addition of the PTEN inhibitor SF1670. Moreover, the number of apoptotic myeloma cells was remarkably larger after transfection with the miR-32 inhibitor, while it was remarkably smaller after addition of the PTEN inhibitor SF1670. The expressions of pro-apoptotic proteins Bak and caspase-9 in myeloma cells were significantly increased after transfection with the miR-32 inhibitor (p<0.05), and significantly decreased after addition of the PTEN inhibitor SF1670, while the expressions of anti-apoptotic proteins Bcl-2 and survivin were opposite to those of Bak and caspase-9. CONCLUSIONS: MiR-32 targeting PTEN will have certain effects on the proliferation and apoptosis of myeloma cells.

Modulation effect of Lactobacillus acidophilus KLDS 1.0738 on gut microbiota and TLR4 expression in ß-lactoglobulin-induced allergic mice model.

OBJECTIVES: ß-lactoglobulin (ß-Lg)-sensitized mice model was employed to investigate the correlation between Lactobacillus acidophilus KLDS 1.0738 (Lap KLDS 1.0738) modulating gut microbiota and inducting Toll-like receptors (TLRs) expression. METHODS: The alterations of mice fecal microbiota were analyzed by 16S rRNA gene sequencing. The serum cytokines production and TLR4/NF-κB mRNA expression in the colon tissues were measured by ELISA kit and quantitative RT-PCR, respectively. RESULTS: The results showed that Lap KLDS 1.0738 pretreatment attenuated ß-Lg-induced hypersensitivity, accompanied with a diminished expression of TLR4/NF-κB signaling. Moreover, oral administration of Lap KLDS 1.0738 improved the richness and diversity of fecal microbiota, which was characterized by fewer Proteobacteria phylum and Helicobacteraceae family, and higher Firmicutes phylum and Lachnospiraceae family than allergic group. Notably, TLR4/NF-κB expression was positively correlated with the family of Helicobacteraceae in allergic group, but negatively correlated with the family of Lachnospiraceae, Ruminococcaceae and anti-inflammatory cytokines level. A significant positive correlation was observed between TLR4/NF-κB expression and the production of histamine, total IgE and pro-inflammatory cytokines. CONCLUSIONS: Intake of Lap KLDS 1.0738 can influence the gut bacterial composition, which might result in recognizing TLRs signaling so as to inhibit allergic response.

[Knockdown of mediator complex subunit 19 suppresses the migration and invasion and epithelial-mesenchymal transition in prostate cancer PC3 cells].

Objective: To studythe effect of lentivirus-mediated inhibition of Med19 on cell migration andinvasion in the PC3 cells, and explore the mechanism of epithelial-mesenchymal transition transformation. Methods: The lentivirus vectors containing small interferingRNA(siRNA) targeting Medl9 gene were constructed and transfected to PC3 cells.Quantitative real-time PCR(qRT-PCR) and Western blot analysis were used to detect the Medl9 expression in the siRNA group(PC3-Med 19-siRNA cells)and the NC group(PC3-Med 19-sc cells) at 72h after the transfection.The cell mobility,migration and invasion ability of PC3 cells were respectively measured by Boyden migration and woun-healing assay. The expression of E-Cadherin, N-Cadherin, Vimentin, ZEB2, Snail-1, and Snail-2 mRNA were detected by using qRT-PCR. Results: The expression of Medl9 mRNA in PC3-Med 19-siRNA cells was lower than that in PC3-Med 19-scRNA cells(P<0.01). The number of migrated cells and invaded cells were significantly decreased in PC3-Med 19-siRNA cells(P<0.01). The expression of N-Cadherin, Vimentin, ZEB2, Snail-1, and Snail-2 mRNA were remarkablylower and E-Cadherin was higher in PC3-Med 19-siRNA cells. Conclusion: Med 19 inhibitioncouldreduce migration abilityof prostate cancer PC3 cells by epithelial-mesenchymal transition.

Immune efficacy of a porcine circovirus type 2 vaccine purified using Gram-positive enhancer matrix surface display technology.

AIMS: Purification of porcine circovirus type 2 (PCV2) using Gram-positive enhancer matrix (GEM) surface display technology and immunogenicity evaluation of the purified antigen. METHODS AND RESULTS: A recombinant bifunctional protein containing a protein anchor domain and a 'virus anchor' domain was designed as a protein linker (PL) between PCV2 and GEM particles. By incubating with PL and GEM particles sequentially, PCV2 could be purified and enriched through a simple centrifugation process with GEM surface display technology. Our data showed that one unit (2·5 × 109 particles) of GEM particles with 80 µg PL could purify 100 ml of PCV2-containing culture supernatant (viral titre: 106·5 TCID50 per ml-1 ) with a recovery rate up to 99·6%. The impurity removal efficiency of this method, calculated according to decreased total protein content during purification, was approximately 98%. Furthermore, in vivo experimentation showed that piglets immunized with purified PCV2 could elicit strong immune responses to prevent against PCV2 infection. CONCLUSION: Porcine circovirus type 2 could be efficiently purified and enriched with GEM display technology via a crucial PL, and the purified PCV2 could elicit effective immune responses against PCV2 infection. SIGNIFICANCE AND IMPACT OF THE STUDY: The GEM-based purification method established here is cost-efficient and high-throughput, and may represent a promising large-scale purification method for PCV2 vaccine production.

A three-dimensional metal-organic framework for a guest-free ultra-low dielectric material.

A three-dimensional metal-organic framework compound [NH2(CH3)2]2[Zn3(bpdc)4]·3DMF (1) shows two step dielectric relaxation and its guest-free framework (1') possesses an ultra-low κ value of 1.80 (at 100 kHz, it is the lowest value for MOFs reported to date) over a wide temperature range and high thermal stability.

[Biomechanics changes of lumbar spine caused by foraminotomy via percutaneous transforaminal endoscopic lumbar discectomy].

Objective: To analyze the biomechanics changes of lumbar spine caused by foraminotomy via percutaneous transforaminal endoscopic lumbar discectomy using the finite element method. Methods: Three healthy adult males (aged 35.6 to 42.3 years) without spinal diseases were enrolled in this study and 3D-CT scans were carried out to obtain the parameters of lumbar spine. Mimics software was applied to build a 3D finite element model of lumbar spine. Graded resections (1/4, 2/4, 3/4 and 4/4) of the left superior articular process of L(5) were done via percutaneous transforaminal endoscopic lumbar discectomy. Then, the pressure of the L(4/5) right facets, the pressure of the L(4/5) intervertebral disc and the motion of lumbar spine were recorded after simulating the normal flexion and extension, lateral flexion and rotation of the lumbar spine model during different resections. The data were compared among groups with analysis of variance. Results: Comparing with the normal group, after 1/4 resection of the left superior articular process of L(5), the pressure of the L(4/5) right facets showed significant differences during left lateral flexion and rotation of lumbar spine (q=8.823, 8.248, both P<0.05); and the pressure of L(4/5) intervertebral disc also changed significantly during extension and right rotation of lumbar spine (q=6.918, 6.438, both P<0.05); the motion of lumbar spine showed obvious differences during right lateral flexion and rotation (q=6.845, 7.772, 13.58, all P<0.05). Comparing with the normal group, after 2/4 resection of the left superior articular process of L(5), the pressure of the L(4/5) right facets presented significant differences during all conditions (q=5.670-17.830, all P<0.05); the pressure of L(4/5) intervertebral disc changed significantly during flexion, extension, lateral flexion and right rotation (q=5.260, 17.150, 5.727, 8.890, 15.660, all P<0.05); the motion of lumbar spine also existed differences during extension, lateral flexion and rotation (q=9.106, 5.431, 12.060, 11.160, 17.260, all P<0.05). However, after 3/4 resections, the pressure of the L(4/5) right facets, the pressure of the L(4/5) intervertebral disc and the motion of lumbar spine presented differences during all conditions when compared with those in normal group (q=6.303-25.48, all P<0.05). After 4/4 resections, the pressure of the L(4/5) right facets and the pressure of the L(4/5) intervertebral disc and the motion of lumbar spine showed significant differences during all conditions when compared with those in normal group (q=8.065-45.70, all P<0.05). Conclusions: The biomechanics and the stability of lumbar spine changed partly after 1/4 resection of the superior articular process and obviously after more than 2/4 is resected. The superior articular process should be paid more attention during foraminotomy via percutaneous transforaminal endoscopic lumbar discectomy.

[The application progress of 3D printing technology in ophthalmology].

3D printing is a kind of technology that makes 3D models from computer-aided designs through additive manufacturing, in which successive layers of the material are deposited onto underlying layers to construct 3D objects. In recent years, 3D printing is gradually applied in the field of ophthalmology, such as the cornea, retina, orbital operation, ocular tumor radiotherapy, ocular implants and ophthalmology teaching. This article reviews the application status of 3D printing technology in the basic research and clinical treatment in ophthalmology. (Chin J Ophthalmol, 2018, 54: 72-76).

Collision cross section predictions using 2-dimensional molecular descriptors.

Traditional methods for deriving computationally-generated collision cross sections for comparisons with ion mobility-mass spectrometry data require 3-dimensional energy-minimized structures and are often time consuming, preventing high throughput implementation. Here, we introduce a method to predict ion mobility collision cross sections of lipids and peptide analogs important in prebiotic chemistry and other fields. Using less than 100 2-D molecular descriptors this approach resulted in prediction errors of less than 2%.

Mutational analysis of mitochondrial tRNA genes in patients with lung cancer.

Mutations in mitochondrial tRNA (mt-tRNA) genes have been found to be associated with various diseases including lung cancer. To understand the possible relationship between mtRNA mutations and lung cancer, we sequenced the 22 mt-tRNA genes from 200 lung cancer blood samples, as well as 100 healthy subjects. As a result, five mutations were identified including the tRNAAla T5655C, tRNAArg T10454C, tRNALeu(CUN) A12330G, tRNASer(UCN) T7505C and tRNAThr G15927A. These mutations were absent in the healthy subjects. These mutations and polymorphisms were localized at the highly conserved nucleotides of the corresponding mitochondrial tRNAs, which are critical for the tRNA steady state level and may result in failure in the tRNA metabolism. Moreover, through the application of the pathogenicity scoring system, we found that only the T10454C mutation should be classified as a "neutral polymorphism," while the other mutations were regarded as "definitely pathogenic." Taken together, our data indicate that tRNA genes are the hot-spots for pathogenic mutations associated with lung cancer. Our findings may provide valuable information for pathophysiology, management and genetic counseling of lung cancer.

Association of endothelin-1 and matrix metallopeptidase-9 with metabolic syndrome in middle-aged and older adults.

BACKGROUND: Metabolic syndrome (MetS) contains a cluster of cardiovascular risk factors. People with MetS are more susceptible to cardiovascular disease, diabetes mellitus, and cancer. Endothelin-1 (ET-1) and matrix metallopeptidase-9 (MMP-9) have been implicated in the development of cardiovascular diseases, diabetes mellitus and cancers. This cross-sectional study aimed to examine the association of ET-1 and MMP-9 with MetS in middle-aged and older Hong Kong Chinese adults. METHODS: 149 adults aged 50 to 92 (n = 75 for non-MetS group and n = 74 for MetS group) were examined. All subjects were screened for MetS according to the diagnostic guideline of the United States National Cholesterol Education Program (NCEP) Expert Panel Adult Treatment Panel (ATP) III criteria. Serum levels of ET-1 and MMP-9 were measured. Independent t test was used to detect differences between non-MetS and MetS groups and between subjects with or without certain metabolic abnormality. The association of the serum concentration of MMP-9 and ET-1 with MetS parameters were examined by Pearson's correlation analysis. RESULTS: Serum level of ET-1 is higher in MetS-positive subjects and in subjects with high blood pressure, elevated fasting blood glucose, and central obesity. The serum concentration of MMP-9 is higher in subjects positively diagnosed with MetS and subjects with high blood pressure, elevated fasting blood glucose, low blood high-density lipoprotein-cholesterol (HDL-C), high blood triglycerides, and central obesity. Correlation analyses revealed that serum concentration of ET-1 is positively correlated to systolic blood pressure, waist circumference, fasting blood glucose, and age whereas it is negatively correlated to HDL-C. MMP-9 is positively correlated to systolic blood pressure, waist circumference, fasting blood glucose, and age whereas it is negatively correlated to HDL-C. CONCLUSION: Serum ET-1 is higher in subjects with hypertension, hyperglycemia, central obesity or MetS. Serum MMP-9 is higher in subjects diagnosed with MetS or having either one of the MetS parameters. Both circulating levels of ET-1 and MMP-9 are correlated to systolic blood pressure, waist circumference, fasting blood glucose, HDL-C, and age. Further research is needed to fully dissect the role of ET-1 and MMP-9 in the development of cancers, diabetes and cardiovascular disease in relation to MetS.

Does airway integrated nasal packing after septal surgery improve body oxygenation?

BACKGROUND: Airway integrated nasal packing reportedly improves body oxygenation after septal surgery. This randomized controlled study examined the effect of airway integrated nasal packing on oxygen saturation. METHODS: Eighty patients with septal deviation and hypertrophic turbinate were randomly divided into two groups: Group 1 patients were postoperatively packed with airway integrated Nasopore, and Group 2 patients were postoperatively packed with Nasopore without airway integration. The haemodynamic parameters and SpO2 (oxyhemoglobin saturation levels when measured using pulse oximetry) were sequentially checked. Nasal pain sensations were recorded using a visual analog scale. RESULTS: SpO2 was not significantly different between Groups 1 and 2. Nasal pain levels were significantly higher in Group 1 than in Group 2 at both 4 (p = 0.034) and 6 (p = 0.001) hours postoperatively. There were no significant differences between the two groups in the incidences of septal haematoma, perforation, or bleeding, or in sequentially checked heart rate, mean blood pressure, or respiration rate. CONCLUSION: It was not evident that integrated airways improved the reduction of SpO2. However, Group 1 patients, with integrated airways, had more pain than did Group 2 patients, without integrated airways. EVIDENCE LEVEL: 1b.

The regulatory role of NF-κB in autophagy-like cell death after focal cerebral ischemia in mice.

Autophagy may contribute to ischemia-induced cell death in the brain, but the regulation of autophagic cell death is largely unknown. Nuclear factor kappa B (NF-κB) is a regulator of apoptosis in cerebral ischemia. We examined the hypothesis that autophagy-like cell death could contribute to ischemia-induced brain damage and the process was regulated by NF-κB. In adult wild-type (WT) and NF-κB p50 knockout (p50(-/-)) mice, focal ischemia in the barrel cortex was induced by ligation of distal branches of the middle cerebral artery. Twelve to 24h later, autophagic activity increased as indicated by enhanced expression of Beclin-1 and LC3 in the ischemic core and/or penumbra regions. This increased autophagy contributed to cell injury, evidenced by terminal deoxynucleotidyltransferase (TdT)-mediated dUTP-biotin nick end labeling (TUNEL) co-staining and a protective effect achieved by the autophagy inhibitor 3-methyladenine. The number of Beclin-1/TUNEL-positive cells was significantly more in p50(-/-) mice than in WT mice. Neuronal and vascular cell death, as determined by TUNEL-positive cells co-staining with NeuN or Collagen IV, was more abundant in p50(-/-) mice. Immunostaining of the endothelial cell tight junction marker occludin revealed more damage to the blood-brain barrier in p50(-/-) mice. Western blotting of the peri-infarct tissue showed a reduction of Akt-the mammalian target of rapamycin (mTOR) signaling in p50(-/-) mice after ischemia. These findings provide the first evidence that cerebral ischemia induced autophagy-like injury is regulated by the NF-κB pathway, which may suggest potential treatments for ischemic stroke.

Use of tunable nanopore blockade rates to investigate colloidal dispersions.

Tunable nanopores fabricated in elastomeric membranes have been used to study the dependence of ionic current blockade rate on the concentration and electrophoretic mobility of particles in aqueous suspensions. A range of nanoparticle sizes, materials and surface functionalities has been tested. Using pressure-driven flow through a pore, the blockade rate for 100 nm carboxylated polystyrene particles was found to be linearly proportional to both transmembrane pressure (between 0 and 1.8 kPa) and particle concentration (between 7 × 10(8) and 4.5 × 10(10) ml( - 1)). This result can be accurately modelled using Nernst-Planck transport theory, enabling measurement of particle concentrations. Using only an applied potential across a pore, the blockade rates for carboxylic acid and amine coated 500 and 200 nm silica particles were found to correspond to changes in their mobility as a function of the solution pH. Scanning electron microscopy and confocal microscopy have been used to visualize changes in the tunable nanopore geometry in three dimensions as a function of applied mechanical strain. The pores were conical in shape, and changes in pore size were consistent with ionic current measurements. A zone of inelastic deformation adjacent to the pore has been identified as important in the tuning process.

Rapid alphabeta TCR-mediated responses in gammadelta T cells transduced with cancer-specific TCR genes.

Adoptive T-cell transfer of in vitro cultured T cells derived from cancer patients with naturally developed immune responses has met with some success as an immunotherapeutic approach, although only a limited number of patients showed spontaneous immune responses. To find alternative ways, such as cancer-specific T-cell receptor (TCR) gene transfer, in preparation for sufficient numbers of antigen-specific T cells is an important issue in the field of adoptive T-cell therapy. Given the inherent disadvantage of alphabeta TCR transfer to other alphabeta T cells, namely the possible formation of mixed TCR heterodimers with endogenous alpha or beta TCR, we employed gammadelta T cells as a target for retroviral transfer of cancer-specific TCR and examined whether gammadelta T cells were useful as an alternative population for TCR transfer. Although retroviral transduction to gammadelta T cells with TCR alphabeta genes alone, isolated from a MAGE-A4(143-151)-specific alphabeta CD8(+) cytotoxic T lymphocyte (CTL) clone, did not provide sufficient affinity to recognize major histocompatibility (MHC)-peptide complexes due to the lack of CD8 co-receptor, gammadelta T cells co-transduced with TCR alphabeta and CD8 alphabeta genes acquired cytotoxicity against tumor cells and produced cytokines in both alphabeta- and gammadelta-TCR-dependent manners. Furthermore, alphabeta TCR and CD8-transduced gammadelta T cells, stimulated either through alphabeta TCR or gammadelta TCR, rapidly responded to target cells compared with conventional alphabeta T cells, reminiscent of gammadelta T cells. We propose alphabeta TCR-transduced gammadelta T cells as an alternative strategy for adoptive T-cell transfer.