Experimental Limits on Solar Reflected Dark Matter with a New Approach on Accelerated-Dark-Matter-Electron Analysis in Semiconductors.

Recently a dark matter-electron (DM-electron) paradigm has drawn much attention. Models beyond the standard halo model describing DM accelerated by high energy celestial bodies are under intense examination as well. In this Letter, a velocity components analysis (VCA) method dedicated to swift analysis of accelerated DM-electron interactions via semiconductor detectors is proposed and the first HPGe detector-based accelerated DM-electron analysis is realized. Utilizing the method, the first germanium based constraint on sub-GeV solar reflected DM-electron interaction is presented with the 205.4 kg·day dataset from the CDEX-10 experiment. In the heavy mediator scenario, our result excels in the mass range of 5-15 keV/c^{2}, achieving a 3 orders of magnitude improvement comparing with previous semiconductor experiments. In the light mediator scenario, the strongest laboratory constraint for DM lighter than 0.1 MeV/c^{2} is presented. The result proves the feasibility and demonstrates the vast potential of the VCA technique in future accelerated DM-electron analyses with semiconductor detectors.

Impaired local Vitamin D3 metabolism contributes to IL-36g overproduction in epithelial cells in chronic rhinosinusitis with nasal polyps.

BACKGROUND: Vitamin D (VD) possesses immunomodulatory properties, but its role in chronic rhinosinusitis with nasal polyps (CRSwNP) remains poorly studied. Herein, we aim to explore the regulation and function of VD3 in CRSwNP. METHODS: 25-hydroxyvitamin D3 (25VD3) levels in serum and tissue lysates were detected by ELISA. The expression of VD receptor (VDR) and cytochrome P450 family 27 subfamily B member 1 (CYP27B1), the enzyme that converts 25VD3 to the active 1,25-hydroxyvitamin D3 (1,25VD3), and their expression regulation in human nasal epithelial cells (HNECs) were studied by RT-PCR, western blotting, immunofluorescence, and flow cytometry. RNA sequencing was performed to identify genes regulated by 1,25VD3 in HNECs. HNECs and polyp tissue explants were treated with 1,25VD3, 25VD3, and dexamethasone. RESULTS: 25VD3 levels in serum and nasal tissue lysates were decreased in patients with eosinophilic and noneosinophilic CRSwNP than control subjects. The expression of VDR and CYP27B1 were reduced in eosinophilic and noneosinophilic CRSwNP, particularly in nasal epithelial cells. VDR and CYP27B1 expression in HNECs were downregulated by interferon y and poly (I:C). Polyp-derived epithelial cells demonstrated an impaired ability to convert 25VD3 to 1,25VD3 than control tissues. 1,25VD3 and 25VD3 suppressed IL-36y production in HNECs and polyp tissues, and the effect of 25VD3 was abolished by siCYP27B1 treatment. Tissue 25VD3 levels negatively correlated with IL-36y expression and neutrophilic inflammation in CRSwNP. CONCLUSION: Reduced systemic 25VD3 level, local 1,25VD3 generation and VDR expression result in impaired VD3 signaling activation in nasal epithelial cells, thereby exaggerating IL-36y production and neutrophilic inflammation in CRSwNP.

[Clinical, endoscopic, and pathological analyses of 14 cases of gastric adenocarcinoma of the fundic gland type].

Objective: Gastric adenocarcinoma of the fundic gland type (GA-FG) is rare and often occurs in patients who are not infected with Helicobacter pylori. The current study analyzed and summarized the clinical, endoscopic, and pathological features of GA-FG, in an effort to improve its diagnosis. Methods: Patients who were diagnosed with GA-FG and treated with endoscopic submucosal dissection (ESD) resection at the Department of Gastroenterology, First Affiliated Hospital of Zhejiang Chinese Medical University from January 1st 2020 to October 1st 2022 were included in the study. Their clinical manifestations, endoscopic features, pathological immunohistochemistry, and other characteristics were analyzed. Results: A total of 14 patients with GA-FG were included in the study, 5 males and 9 females, with a mean age of 59 years. Most had no substantial clinical manifestations. Twelve patients were H. pylori-negative, all patients underwent ESD resection, and all patients survived during the follow-up period of 13±9 months. Eleven patients had postoperative endoscopic follow-up records, and no recurrence was detected. Fifteen lesions were detected (2 were present in 1 patient). Twelve were located in the upper 1/3 of the stomach, 10 were ≤ 1 cm in diameter, 12 had a morphology of type 0-Ⅱa, 8 had visible discoloration changes, and 12 had visible vasodilation on the surface. Magnified endoscopy and narrow-band imaging indicated that 12 of the lesions had enlarged marginal crypt epithelium, without any obvious microvascular pattern abnormalities and no obvious borderline. After resection the pathological specimens were all without vascular infiltration, and there was no atrophy of the mucosa at the edge of the lesion. In immunohistochemistry analyses MUC-2 was negative in all cases. MUC5AC was negative in 11 cases, MUC-6 was positive in all cases, and Ki-67 was ≤ 5% in 12 cases. Conclusions: GA-FG is a newly identified type of gastric cancer with low malignancy and a good prognosis. Characteristic discoloration and surface dilated vessels are often evident endoscopically. Enlarged marginal crypt epithelium and no visible boundary lines are often apparent in magnification endoscopy and narrow band imaging.

[Genetic diagnosis of microcephaly].

Objective: To explore the diagnostic value of chromosome karyotype analysis, chromosomal microarray analysis (CMA) and whole exome sequencing (WES) in microcephaly. Methods: A total of 9 cases of microcephaly fetuses diagnosed by prenatal ultrasound or children with microcephaly diagnosed after birth were selected from the Sixth Affiliated Hospital of Guangzhou Medical University from January 2014 to August 2022.Karyotype analysis and/or CMA were used to detect. The cases with negative karyotype analysis and CMA results were further sequenced by trio-based WES (Trio-WES). Then the coding genes contained in the pathogenic copy number variation (CNV) fragments were analyzed by gene ontology (GO) enrichment. The genes related to the development of the central nervous system contained in the pathogenic CNV and the pathogenic genes found by Trio-WES were combined for gene interaction network analysis. Results: In this study, 9 cases of microcephaly were recruited, with the time of diagnosis ranged from 23 weeks of gestation to 7 years after birth, and the head circumference of fetus or children ranged from 18.3 to 42.5 cm (-7SD to -2SD). Karyotype analysis was detected in all 9 cases and no abnormality result was found. Eight cases were detected by CMA, and one abnormal was found. Five cases were detected by Trio-WES, and two cases were detected with likely pathogenic genes. The GO enrichment analysis of the coding gene in the 4p16.3 microdeletion (pathogenic CNV) region showed that: in biological process, it was mainly concentrated in phototransduction, visible light; in terms of molecular function, it was mainly concentrated in fibroblast growth factor binding; in terms of cell components, it was mainly concentrated in rough endoplasmic reticulum. Gene interaction network analysis suggested that CDC42 gene could interact with CTBP1, HTT and ASPM gene. Conclusions: CMA could be used as a first-line detection technique for microcephaly. When the results of chromosome karyotype analysis and/or CMA are negative, Trio-WES could improve the detection rate of pathogenicity of microcephaly.

Constraints on Sub-GeV Dark Matter-Electron Scattering from the CDEX-10 Experiment.

We present improved germanium-based constraints on sub-GeV dark matter via dark matter-electron (χ-e) scattering using the 205.4 kg·day dataset from the CDEX-10 experiment. Using a novel calculation technique, we attain predicted χ-e scattering spectra observable in high-purity germanium detectors. In the heavy mediator scenario, our results achieve 3 orders of magnitude of improvement for m_{χ} larger than 80 MeV/c^{2} compared to previous germanium-based χ-e results. We also present the most stringent χ-e cross-section limit to date among experiments using solid-state detectors for m_{χ} larger than 90 MeV/c^{2} with heavy mediators and m_{χ} larger than 100 MeV/c^{2} with electric dipole coupling. The result proves the feasibility and demonstrates the vast potential of a new χ-e detection method with high-purity germanium detectors in ultralow radioactive background.

Exotic Dark Matter Search with the CDEX-10 Experiment at China's Jinping Underground Laboratory.

A search for exotic dark matter (DM) in the sub-GeV mass range has been conducted using 205 kg day data taken from a p-type point contact germanium detector of the CDEX-10 experiment at China's Jinping underground laboratory. New low-mass dark matter searching channels, neutral current fermionic DM absorption (χ+A→ν+A) and DM-nucleus 3→2 scattering (χ+χ+A→ϕ+A), have been analyzed with an energy threshold of 160 eVee. No significant signal was found; thus new limits on the DM-nucleon interaction cross section are set for both models at the sub-GeV DM mass region. A cross section limit for the fermionic DM absorption is set to be 2.5×10^{-46} cm^{2} (90% C.L.) at DM mass of 10 MeV/c^{2}. For the DM-nucleus 3→2 scattering scenario, limits are extended to DM mass of 5 and 14 MeV/c^{2} for the massless dark photon and bound DM final state, respectively.

Predicting difficult-to-treat chronic rhinosinusitis by noninvasive biological markers.

BACKGROUND: Previous studies have been limited to the utility of clinical features and invasive nasal mucosal biomarkers in the prediction of chronic rhinosinusitis (CRS) outcomes. This study aimed to identify noninvasive biomarkers associated with difficult- to-treat CRS, enabling physicians to subgroup patients into risk groups for poor outcome before surgery. METHODS: Three hundred and nine CRS patients undergoing endoscopic sinus surgery were finally enrolled. Patients treated with oral or intranasal glucocorticoids within 3 months or 1 month before surgery, respectively, were excluded. Baseline clinical charac- teristics, nasal secretions and peripheral blood samples were collected before surgery. The protein levels of 39 biological mar- kers were detected by the Bio-Plex suspension chip method. Classification and regression tree analysis was applied to establish prediction model for difficult-to-treat CRS determined one year after surgery. A random forest algorithm was used to confirm the discriminating factors that formed the classification tree. RESULTS: In the cohort with nasal secretion sample (n = 189), 21% of CRS patients were diagnosed as difficult-to-treat after 1 year of follow-up. Nasal secretion CCL17 level, hyposmia score, allergic rhinitis comorbidity, and nasal secretion MIP-1ß level were found important predictors of difficult-to-treat CRS. A classification tree separated patients into 5 subgroups leading to an overall predictive accuracy of 94%. However, none of the plasma biological markers were associated with difficult-to-treat CRS in the cohort with blood sample (n = 128). CONCLUSIONS: Patients with difficult-to-treat-CRS were characterized by higher nasal secretion levels of CCL17 and MIP-1ß severe hyposmia and concomitant allergic rhinitis. The classification tree could be useful to identify patients with high risk of poor outcome prior to surgery and offer more personalized interventions. However, since only patients without preoperative steroid treatments were included in this study, the generalization of our predictive model in other patient populations should be conside- red with caution.

[Long-term therapeutic effects and liver fibrosis changes with direct-antiviral therapy in HIV/HCV co-infected patients].

Objective: To investigate the long-term characteristic changes of virus, immune status, and liver fibrosis markers in human immunodeficiency virus (HIV)/hepatitis C virus (HCV) co-infected patients after receiving direct-antiviral agents (DAAs). Methods: HIV/HCV co-infected patients who visited the Guangzhou Eighth People's Hospital, Guangzhou Medical University from May 2014 to December 2019 were selected as the research subjects. The changes of virological response rate, peripheral blood CD4(+)T lymphocyte level and serological markers of liver fibrosis (APRI score and FIB-4 index) were observed during 144 weeks of follow-up course after the end of DAAs treatment. Kruskal-Wallis test was used for statistical approach. Results: A total of 103 cases were included in the study. There were 87 males (87.5%), with a median age of 44 years. Sustained virological response rate at 12 weeks (SVR12) after DAAs treatment was 97.6%, and the SVR during the entire follow-up period was at least 95.9%. Compared with baseline, CD4(+)T lymphocyte count were significantly increased equally at 12 weeks (Z = -2.283, P = 0.022), 24 weeks (Z = -3.538, P < 0.001), 48 weeks (Z = -3.297, P = 0.001), 96 weeks (Z = -3.562, P < 0.001), and 144 weeks (Z = -2.842, P = 0.004). APRI score (Z = -6.394, P < 0.001) and FIB-4 index (Z = -2.528, P = 0.011) were significantly lower than baseline at week 4 of DAAs treatment, and thereafter remained at a low level, without further declination. Conclusion: HIV/HCV co-infected patients can maintain high SVR for a long time, acquire good immune reconstitution, and significantly improve liver fibrosis after DAAs treatment.

2D shear wave elastography combined with age and serum biomarkers prior to kasai surgery predicts native liver survival of biliary atresia infants.

BACKGROUND: The prognosis of patients with biliary atresia (BA) after Kasai portoenterostomy (KPE) varies, and precisely predicting the outcomes of KPE before surgery is still challenging. METHODS: A total of 158 patients who underwent KPE in our hospital were included in this study. The patients in the training cohort were recruited from January 2012 to October 2017 (n = 118), and then, those in the validation cohort were recruited from November 2017 to April 2019 (n = 40). Combined nomogram models were developed based on two-dimensional shear wave elastography (2D SWE) values and other biomarkers. The utility of the proposed models was evaluated by C-index. RESULTS: 2D SWE played a potentially important role in predicting native liver survival (NLS) of BA patients with a C-index of 0.69 (0.63 to 0.75) in the training cohort and 0.76 (0.67 to 0.85) in the validation cohort. The nomogram A based on 2D SWE values, age, gamma-glutamyl transferase (GGT) and aspartate aminotransferase-to-platelet ratio (APRI) had a better C-index in the training cohort [0.74 (0.68-0.80) vs. 0.66 (0.60-0.73), P = 0.017] and in the validation cohort [0.78 (0.70-0.86) vs. 0.60 (0.49-0.71), P = 0.002] than the nomogram B (without 2D SWE). Using risk score developed from nomogram A, we successfully predicted 88.0% (22/25) of patients in the training cohort and 75.0% (9/12) in the validation cohort to have survival time of less than 12 months after KPE. CONCLUSION: The combined nomogram model based on 2D SWE values, age, GGT and APRI prior to KPE can effectively predict NLS in BA infants.

Direct Detection Constraints on Dark Photons with the CDEX-10 Experiment at the China Jinping Underground Laboratory.

We report constraints on the dark photon effective kinetic mixing parameter (κ) with data taken from two p-type point-contact germanium detectors of the CDEX-10 experiment at the China Jinping Underground Laboratory. The 90% confidence level upper limits on κ of solar dark photon from 205.4 kg-day exposure are derived, probing new parameter space with masses (m_{V}) from 10 to 300 eV/c^{2} in direct detection experiments. Considering dark photon as the cosmological dark matter, limits at 90% confidence level with m_{V} from 0.1 to 4.0 keV/c^{2} are set from 449.6 kg-day data, with a minimum of κ=1.3×10^{-15} at m_{V}=200 eV/c^{2}.

Constraints on Spin-Independent Nucleus Scattering with sub-GeV Weakly Interacting Massive Particle Dark Matter from the CDEX-1B Experiment at the China Jinping Underground Laboratory.

We report results on the searches of weakly interacting massive particles (WIMPs) with sub-GeV masses (m_{χ}) via WIMP-nucleus spin-independent scattering with Migdal effect incorporated. Analysis on time-integrated (TI) and annual modulation (AM) effects on CDEX-1B data are performed, with 737.1 kg day exposure and 160 eVee threshold for TI analysis, and 1107.5 kg day exposure and 250 eVee threshold for AM analysis. The sensitive windows in m_{χ} are expanded by an order of magnitude to lower DM masses with Migdal effect incorporated. New limits on σ_{χN}^{SI} at 90% confidence level are derived as 2×10^{-32}∼7×10^{-35} cm^{2} for TI analysis at m_{χ}∼50-180 MeV/c^{2}, and 3×10^{-32}∼9×10^{-38} cm^{2} for AM analysis at m_{χ}∼75 MeV/c^{2}-3.0 GeV/c^{2}.

Search for Light Weakly-Interacting-Massive-Particle Dark Matter by Annual Modulation Analysis with a Point-Contact Germanium Detector at the China Jinping Underground Laboratory.

We present results on light weakly interacting massive particle (WIMP) searches with annual modulation (AM) analysis on data from a 1-kg mass p-type point-contact germanium detector of the CDEX-1B experiment at the China Jinping Underground Laboratory. Datasets with a total live time of 3.2 yr within a 4.2-yr span are analyzed with analysis threshold of 250 eVee. Limits on WIMP-nucleus (χ-N) spin-independent cross sections as function of WIMP mass (m_{χ}) at 90% confidence level (C.L.) are derived using the dark matter halo model. Within the context of the standard halo model, the 90% C.L. allowed regions implied by the DAMA/LIBRA and CoGeNT AM-based analysis are excluded at >99.99% and 98% C.L., respectively. These results correspond to the best sensitivity at m_{χ}<6 GeV/c^{2} among WIMP AM measurements to date.

A retrospective study of changes of histopathology of nasal polyps in adult Chinese in central China.

BACKGROUND: The factors contributing to the eosinophilic inflammation in chronic rhinosinusitis with nasal polyps (CRSwNP) remain elusive. This study was designed to investigate the inflammatory patterns and tissue remodeling of CRSwNP in patients from central China at two time points over 14 years apart and the influence of age. METHODS: One hundred and eight CRSwNP patients enrolled in 2000 and 2001 (group A), and 134 CRSwNP patients enrolled in 2014 and 2015 (group B) were retrospectively studied. Hematoxylin-eosin stained tissue sections were used to study characteristics of inflammation and tissue remodeling. Immunohistochemistry was used to further evaluate the cells positive for eosinophil cationic protein (ECP), IL-5, IgE, tryptase or myeloperoxidase (MPO). Time- and age-related difference was analyzed. RESULTS: The number of eosinophils and proportion of eosinophilic CRSwNP were increased, whereas the numbers of total inflammatory cells and lymphocytes were decreased in group B as compared with group A. Group B had severer epithelial squamous metaplasia and basement membrane thickening, and a lower number of mucosal glands than group A. Higher numbers of ECP plus, IL-5 plus and IgE plus cells were detected in group B than those in group A. The elderly (60 yrs or older) and non-elderly (less than 60 yrs) had a comparable number of eosinophils and ratio of eosinophilic CRSwNP. CONCLUSION: Eosinophilic inflammation has been significantly augmented over time, which is associated with increased Th2 response and IgE production, and accompanied by exaggerated epithelium remodeling in CRSwNP patients from central China. Age has no significant influence on eosinophilic inflammation.

Comparison of efficacy of fluticasone propionate versus clarithromycin for postoperative treatment of different phenotypic chronic rhinosinusitis: a randomized controlled trial.

BACKGROUND: Chronic rhinosinusitis (CRS) can be divided to CRS without nasal polyps (CRSsNP) and eosinophilic and non-eosinophilic CRS with nasal polyps (CRSwNP). There is little evidence on the efficacy of glucocorticoids and macrolides in different phenotypic patients. The aim of this study was to compare the benefit of glucocorticoids and macrolides following endoscopic sinus surgery (ESS) in different phenotypic CRS. METHODS: This study was a prospective single-blind comparative effectiveness trial. A total of 187 Chinese patients with CRS were stratified to CRSsNP and eosinophilic and non-eosinophilic CRSwNP group and then randomized to receive fluticasone propionate nasal spray at 200 microgram or clarithromycin tablet at 250 mg once daily for 3 months after ESS. Oral prednisone was given as a rescue therapy after the stop of study medication. Patients were assessed before ESS and 1, 3, 6 and 12 months after dosing. Symptom severity was scored by patients using visual analog scale method and endoscopic findings were scored by the senior physician blinded to treatment according to European Position Paper on Rhinosinusitis and Nasal polyps 2012. RESULTS: The total and individual symptom scores, and total and individual endoscopic domain scores were reduced significantly after ESS in both medication groups, whereas no significant difference was observed for two medications at most follow-up visits in each subtype of CRS. No difference in the frequency of subjects with rescue therapy or refractory CRS was found between two medication groups either. CONCLUSIONS: We could not show significant difference of effect between fluticasone propionate and clarithromycin in the post-operative treatment for CRSsNP and eosinophilic and non-eosinophilic CRSwNP patients.

[Construction and analysis of gene co-expression networks in intracranial aneurysm].

Objective: To analyze the expression microarray data in the public databases of intracranial aneurysms (IA) using bioinformatics, and to provide important information for the study of disease mechanisms. Methods: Gene co-expression network was constructed by weighted gene co-expression network analysis (WGCNA) based on the dataset (GSE75436) and pivot genes were identified. Using the online tool DAVID (Database for Annotation, Visualization, and Integrated Discovery) to perform GO function enrichment and KEGG path analysis on modules highly related to IA. Results: Three IA-related modules were screened out, and 14 pivot genes (COL3A1, SPARC, CDH11, COL5A1, HOPX, CLEC11A, GALNT10, ADAMTS2, CEMIP, KIAA1755, COL11A1, ZIC2, CDKN2A, and LINC00460) in the brown module were identified; the analysis of GO showed that the brown module was mainly enriched in extracellular matrix organization, extracellular matrix organization, cell adhesion and other biological processes; the analysis of KEGG indicated that the brown module involved in ECM-receptor interaction, Focal adhesion, protein digestion and absorption, PI3K-Akt signaling pathway. Conclusion: Based on WGCNA, we identified modular and pivotal genes that are critical to the development of IA, and they may become potential biomarkers and/or therapeutic targets.

Limits on Light Weakly Interacting Massive Particles from the First 102.8 kg×day Data of the CDEX-10 Experiment.

We report the first results of a light weakly interacting massive particles (WIMPs) search from the CDEX-10 experiment with a 10 kg germanium detector array immersed in liquid nitrogen at the China Jinping Underground Laboratory with a physics data size of 102.8 kg day. At an analysis threshold of 160 eVee, improved limits of 8×10^{-42} and 3×10^{-36} cm^{2} at a 90% confidence level on spin-independent and spin-dependent WIMP-nucleon cross sections, respectively, at a WIMP mass (m_{χ}) of 5 GeV/c^{2} are achieved. The lower reach of m_{χ} is extended to 2 GeV/c^{2}.

Multidimensional endotypes of chronic rhinosinusitis and their association with treatment outcomes.

BACKGROUND: The expression of chronic rhinosinusitis (CRS) is multidimensional. Disease heterogeneity in patients with CRS remains poorly understood. This study aimed to identify endotypes of CRS using cluster analysis by integrating multidimensional characteristics and to explore their association with treatment outcomes. METHODS: A total of 28 clinical variables and 39 mucosal cellular and molecular variables were analyzed using principal component analysis. Cluster analysis was performed on 246 prospectively recruited Chinese CRS patients with at least 1-year postoperative follow-up. Difficult-to-treat CRS was characterized in each generated cluster. RESULTS: Seven subject clusters were identified. Cluster 1 (13.01%) was comparable to the classic well-defined eosinophilic CRS with polyps, having severe disease and the highest proportion of difficult-to-treat CRS. Patients in cluster 2 (16.26%) and cluster 4 (13.82%) had relatively lower proportions of presence of polyps and presented mild inflammation with moderate proportions of difficult-to-treat cases. Subjects in cluster 2 were highly atopic. Cluster 3 (7.31%) and cluster 6 (21.14%) were characterized by severe or moderate neutrophilic inflammation, respectively, and with elevated levels of IL-8 and high proportions of difficult-to-treat CRS. Cluster 5 (4.07%) was a unique group characterized by the highest levels of IL-10 and lacked difficult-to-treat cases. Cluster 7 (24.39%) demonstrated the lowest symptom severity, a low proportion of difficult-to-treat CRS, and low inflammation load. Finally, we found that difficult-to-treat CRS was associated with distinct clinical features and biomarkers in the different clusters. CONCLUSIONS: Distinct clinicopathobiologic clusters of CRS display differences in clinical response to treatments and characteristics of difficult-to-treat CRS.

[The mechanism of nicotine on human bronchial smooth muscle cell contraction].

Objective: To investigate the molecular mechanism of contractility dysfunction of human bronchial smooth muscle cells induced by nicotine. Methods: Primary human bronchial smooth muscle cells were cultured in vitro. The cells were divided into a control group and a nicotine group which was treated with 10(-5) mol/L nicotine for 48 h and transfected with or without α7nAChR-siRNA (The siNC group, siNC + nicotine group and siα7nAChR + nicotine group). The effects of nicotine on the cell contractile function were examined by collagen gel shrinkage assay. The expressions of α7nAChR and TRPC6 protein in nicotine-treated human bronchial smooth muscle cells were detected by Western blotting. The change of intracellular calcium concentration by nicotine was detected by calcium ion imaging system.Data were analyzed by t test or single factor analysis of variance. Results: The area of collagen gel in the nicotine group (24±8)% was significantly lower than that in the control group (59±14)% (t=3.78, P<0.05). Compared with the control group, the expression of α7nAChR protein in nicotine-induced group (173±16)% was significantly higher than that of controls 100±0)%, t=-6.848, P<0.05. Compared with the siNC group [(72±10)%, (0.79±0.07), (0.41±0.04) and (0.17±0.02) respectively], the collagen gel area of siNC + nicotine group was significantly reduced by (37±10)%. However, the basal calcium level (1.04±0.02), store operated calcium entry level (SOCE, 0.68±0.03) and receptor operated calcium entry level (ROCE, 0.36±0.02) were remarkably elevated in the nicotine treated group (all P<0.05). Furthermore, compared with siNC + nicotine group, the area of collagen gel in siα7nAChR + nicotine group was significantly increased (62±10)%, and the basal calcium level (0.78±0.06), SOCE level (0.39±0.05) and ROCE level (0.15±0.02) were significantly reduced (all P<0.05). Conclusions: Nicotine can increase the expression of TRPC6 protein, SOCE and ROCE level, and increase the intracellular calcium concentration by upregulating the expression of α7nAChR protein, thereby promoting smooth muscle cell contraction.

Interferon-γ-induced insufficient autophagy contributes to p62-dependent apoptosis of epithelial cells in chronic rhinosinusitis with nasal polyps.

BACKGROUND: Autophagy is a lysosomal degradation pathway that is essential for cell survival, differentiation, and homeostasis. This study aimed to investigate the contribution of autophagy to the pathogenesis of CRS with nasal polyps (CRSwNP). METHODS: The expression of autophagic proteins [microtubule-associated protein 1 light chain 3B (LC3B)-II, autophagy-related proteins (Atg), and Beclin 1], substrate proteins (p62 and ubiquitinated proteins), and apoptotic signaling molecules [cysteine-aspartic protease-3 and cysteine-aspartic protease-8, and poly-ADP-ribose polymerase] in the sinonasal mucosa and nasal epithelial cells (NECs) was detected by immunohistochemistry and Western blotting. Autophagic vacuoles were observed with transmission electron microscopy. BEAS-2B cells and NECs were treated with rapamycin, bafilomycin A1, or various cytokines. In some experiments, cultured NECs were transfected with small interfering RNA targeting p62 (sip62) or Atg5 (siAtg5). Cultured cells were analyzed with Western blotting and flow cytometry. RESULTS: Although autophagic protein expression and autophagic vacuole formation were increased in both eosinophilic and noneosinophilic CRSwNP, particularly in NECs, there was also an up-regulation of substrate proteins and apoptotic signaling molecules. IFN-γ, but not IL-4, IL-13, or IL-17A, simultaneously enhanced LC3B-II and p62 levels as well as cell apoptosis in BEAS-2B cells and/or normal NECs. Bafilomycin A1 up-regulated the levels of LC3B-II and p62 in polyp NECs and IFN-γ-treated normal NECs. IFN-γ-induced apoptosis of normal NECs was exaggerated by bafilomycin A1 and siAtg5. Sip62 suppressed apoptosis of polyp NECs and IFN-γ-treated NECs. IFN-γ protein levels were increased in both eosinophilic and noneosinophilic CRSwNP. CONCLUSIONS: IFN-γ induces activated but insufficient autophagy and thus contributes to a degree to p62-dependent apoptosis of NECs in CRSwNP.

Association between single nucleotide polymorphisms in AKT1 and the risk of prostate cancer in the Chinese Han population.

AKT1, also known as v-akt murine thymoma viral oncogene homolog 1, is involved in the regulation of cell-survival and anti-apoptotic activities, which may affect the pathogenesis of various cancers. However, the association between genetic variants of AKT1 and the risk of developing prostate cancer has not been investigated before. This study investigated the associations between three polymorphisms (rs1130214, rs3730358, and rs2494732) in AKT1 and the risk of development of prostate cancer in the Chinese Han population. Sequenom MassARRAY & iPLEX technology were used to genotype these polymorphisms in 493 Chinese Han patients with prostate cancer and 309 age-matched healthy individuals. Compared to the CC genotype of the rs3730358 polymorphism, the CT genotype of the same polymorphism was strongly associated with a decreased risk of prostate cancer (OR = 0.617, 95%CI = 0.390-0.976, P = 0.037). However, there was no significant difference between the allele frequency of the rs3730358 polymorphism and those of the other two polymorphisms (P > 0.05). Moreover, no significant difference was found in the haplotype analysis (P > 0.05). Our study found that the variant genotype CT of rs3730358 of AKT1 was associated with a decreased risk of prostate cancer, which suggested that this polymorphism could play an important role in the development of the disease.