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Background: Chronic Rhinosinusitis is a common disease in children. The main function of CFTR is to maintain the thickness of the mucous layer on the surface of the nasal mucosa. CFTR disease-causing variant can cause CFTR protein dysfunction and induce or aggravate chronic infection. However, the carrying status of the CFTR variants in the Chinese population is not clear. Objective: To study the frequency and variants of CFTR in Chinese children with CRS and to analyze the CFTR variants and the clinical characteristics and susceptibility to CRS. Methods: Whole Exome Sequencing was performed to analyze the CFTR genes in a total of 106 CRS children from the Chinese mainland area. The CFTR variants, frequency and clinical data were summarized and analyzed. Results: A total of 31 CFTR variants were detected, of which the carrying rate of 7 sites was significantly higher than that of the population database. 88 patients carried more than 2 variants. 37 people carried variants (MAF

Abstract Background Prostate cancer (PCa), one of the common malignant tumors, is the second leading cause of cancer-related deaths in men. The circadian rhythm plays a critical role in disease. Circadian disturbances are often found in patients with tumors and enable to promote tumor development and accelerate its progression. Accumulating evidence suggests that the core clock gene NPAS2 (neuronal PAS domain-containing protein 2) has been implicated in tumors initiation and progression. However, there are few studies on the association between NPAS2 and prostate cancer. The purpose of this paper is to investigate the impact of NPAS2 on cell growth and glucose metabolism in prostate cancer. Methods Quantitative real-time PCR (qRT-PCR), immunohistochemical (IHC) staining, western blot, GEO (Gene Expression Omnibus) and CCLE (Cancer Cell Line Encyclopedia) databases were used to analyze the expression of NPAS2 in human PCa tissues and various PCa cell lines. Cell proliferation was assessed using MTS, clonogenic assays, apoptotic analyses, and subcutaneous tumor formation experiments in nude mice. Glucose uptake, lactate production, cellular oxygen consumption rate and medium pH were measured to examine the effect of NPAS2 on glucose metabolism. The relation of NPAS2 and glycolytic genes was analyzed based on TCGA (The Cancer Genome Atlas) database. Results Our data showed that NPAS2 expression in prostate cancer patient tissue was elevated compared with that in normal prostate tissue. NPAS2 knockdown inhibited cell proliferation and promoted cell apoptosis in vitro and suppressed tumor growth in a nude mouse model in vivo. NPAS2 knockdown led to glucose uptake and lactate production diminished, oxygen consumption rate and pH elevated. NPAS2 increased HIF-1A (hypoxia-inducible factor-1A) expression, leading to enhanced glycolytic metabolism. There was a positive correlation with the expression of NPAS2 and glycolytic genes, these genes were upregulated with overexpression of NPAS2 while knockdown of NPAS2 led to a lower level. Conclusion NPAS2 is upregulated in prostate cancer and promotes cell survival by promoting glycolysis and inhibiting oxidative phosphorylation in PCa cells.

ABSTRACT Importance The safety and efficacy of the bath‐plug technique for the closure of cerebrospinal fluid (CSF) leaks in children remain unknown. Objective We undertook this study to ascertain whether the bath‐plug technique was safe and effective for the repair of CSF leaks. Methods We retrospectively reviewed patients who underwent endoscopic repair of CSF leaks with the fat graft as a plug‐in at Beijing Children's Hospital from March 2016 to May 2020. Demographic data, medical history, defect sites and sizes, interventions, and clinical outcomes were analyzed. One representative clinical case was additionally selected to highlight the procedure and the healing process. Results A total of 18 pediatric patients were included in this study. The group was composed of 11 boys and seven girls, aged from 5 to 123 months. The etiologies included congenital CSF leaks (n = 9) and head trauma (n = 9). Among all patients, 12 fistulas (66.7%) were located at the cribriform plate area, two (11.1%) at the roof of the ethmoid sinuses, two (11.1%) in the sphenoid sinus, and two (11.1%) at the frontal sinus. The maximum diameters of fistulas ranged from 5 to 20 mm, with a median value of 8 mm. Encephaloceles were identified in 14 (77.8%) patients. No hydrocephalus was recognized. All CSF leaks were successfully repaired with a bath‐plug technique. Follow‐up ranged from 50 to 70 months. No surgical complications were encountered in any patient. Interpretation Bath‐plug technique is safe and reliable for the endoscopic management of CSF leaks in children. Meticulous peri‐operative preparations are important for pediatric patients.

Abstract The hypoxia of the tumor microenvironment (TME) seriously restricts the photodynamic therapy (PDT) effect of conventional type‐II photosensitizers, which are highly dependent on O2. In this work, a new type‐I photosensitizer (TPE‐TeV‐PPh3) consisting of a tetraphenylethylene group (TPE) as a bioimaging moiety, triphenyl‐phosphine (PPh3) as a mitochondria‐targeting group, and telluroviologen (TeV2+) as a reactive oxygen species (O2•−, •OH) generating moiety is developed. The luminescence intensity of TPE‐TeV‐PPh3 increased significantly after specific oxidation by excess H2O2 in the TME without responding to normal tissues via the formation of Te═O bond, which can be used for monitoring abnormal H2O2, positioning, and imaging of tumors. TPE‐TeV‐PPh3 with highly reactive radicals generation and stronger hypoxia tolerance realizes efficient cancer cell killing under hypoxic conditions, achieving 88% tumor growth inhibition. Therefore, TPE‐TeV‐PPh3 with low phototoxicity in normal tissue achieves tumor imaging and effective PDT toward solid tumors in response to high concentrations of H2O2 in the TME, which provides a new strategy for the development of type‐I photosensitizers.

HMGB1 is a key late inflammatory mediator upregulated during air-pollution-induced oxidative stress. Extracellular HMGB1 accumulation in the airways and lungs plays a significant role in the pathogenesis of inflammatory lung injury. Decreasing extracellular HMBG1 levels may restore innate immune cell functions to protect the lungs from harmful injuries. Current therapies for air-pollution-induced respiratory problems are inadequate. Dietary antioxidants from natural sources could serve as a frontline defense against air-pollution-induced oxidative stress and lung damage. Here, a standardized botanical antioxidant composition from Scutellaria baicalensis and Acacia catechu was evaluated for its efficacy in attenuating acute inflammatory lung injury and sepsis. Murine models of disorders, including hyperoxia-exposed, bacterial-challenged acute lung injury, LPS-induced sepsis, and LPS-induced acute inflammatory lung injury models were utilized. The effect of the botanical composition on phagocytic activity and HMGB1 release was assessed using hyperoxia-stressed cultured macrophages. Analyses, such as hematoxylin-eosin (HE) staining for lung tissue damage evaluation, ELISA for inflammatory cytokines and chemokines, Western blot analysis for proteins, including extracellular HMGB1, and bacterial counts in the lungs and airways, were performed. Statistically significant decreases in mortality (50%), proinflammatory cytokines (TNF-α, IL-1β, IL-6) and chemokines (CINC-3) in serum and bronchoalveolar lavage fluid (BALF), and increased bacterial clearance from airways and lungs; reduced airway total protein, and decreased extracellular HMGB1 were observed in in vivo studies. A statistically significant 75.9% reduction in the level of extracellular HMGB1 and an increase in phagocytosis were observed in cultured macrophages. The compilations of data in this report strongly suggest that the botanical composition could be indicated for oxidative-stress-induced lung damage protection, possibly through attenuation of increased extracellular HMGB1 accumulation.

Background: The associations between long-term exposure to ozone (O3) and respiratory diseases are well established. However, its association with cardiovascular disease (CVD) remains controversial. In this study, we examined the associations between O3 and the prevalence of hypertension and blood pressure, and the mediation effects of body mass index (BMI) in Chinese middle-aged and older adults. Methods: In this national cross-sectional study, we estimated the O3 exposure of 12,028 middle-aged and older adults from 126 county-level cities in China, using satellite-based spatiotemporal models. Generalized linear mixed models were used to evaluate the associations of long-term exposure to O3 with hypertension and blood pressure, including systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), and pulse pressure (PP). Mediation effect models were applied to examine the mediation effects of BMI among O3-induced hypertension and elevated blood pressure. Results: Each 10 μg/m3 increase in O3 concentration was significantly associated with an increase of 13.7% (95% confidence interval (CI): 4.8%, 23.3%) in the prevalence of hypertension, an increase of 1.128 mmHg (95% CI: 0.248, 2.005), 0.679 mmHg (95% CI: 0.059, 1.298), 0.820 mmHg (95%CI: 0.245, 1.358) in SBP, DBP, and MAP, respectively. Mediation effect models showed that BMI played 40.08%, 37.25%, 39.95%, and 33.51% mediation roles in the effects of long-term exposure to O3 on hypertension, SBP, DBP, and MAP, respectively. Conclusions: Long-term exposure to O3 can increase the prevalence of hypertension and blood pressure levels of middle-aged and older adults, and an increase of BMI would be an important modification effect for O3-induced hypertension and blood pressure increase.

Over the past two decades, there has been a tendency toward early diagnosis of prostate cancer due to raised awareness among the general public and professionals, as well as the promotion of prostate-specific antigen (PSA) screening. As a result, patients with prostate cancer are detected at an earlier stage. Due to the risks of urine incontinence, erectile dysfunction, etc., surgery is not advised because the tumor is so small at this early stage. Doctors typically only advise active surveillance. However, it will bring negative psychological effects on patients, such as anxiety. And there is a higher chance of cancer progression. Focal therapy has received increasing attention as an alternative option between active monitoring and radical therapy. Due to its minimally invasive, oncological safety, low toxicity, minimal effects on functional outcomes and support by level 1 evidence from the only RCT within the focal therapy literature, photodynamic treatment (PDT) holds significant promise as the focal therapy of choice over other modalities for men with localized prostate cancer. However, there are still numerous obstacles that prevent further advancement. The review that follows provides an overview of the preclinical and clinical published research on PDT for prostate cancer from 1999 to the present. It focuses on clinical applications of PDT and innovative techniques and technologies that address current problems, especially the use of nanoparticle photosensitizers in PDT of prostate cancer.

There are growing interests in developing novel gut modifier feed additives and alternative therapeutics to replace antimicrobials to enhance efficiency of nutrient utilization and to address the antimicrobial resistance threat to public health facing the global pork production. Biological mechanisms of supplementing lactose for enhancing weanling pig growth and nitrogen utilization are unclear. Thus, this study was prompted to determine effects of dietary supplementation of 3 prebiotics and oat β-glucan vs. a sub-therapeutic antibiotic on growth performance, whole-body protein utilization status, the apparent total tract dry matter (DM) and lactose digestibility in weanling pigs fed corn and soybean meal (SBM)-based diets. Six experimental diets were formulated with corn (40%), SBM (28%) and supplemented with dried whey powder (20%) and fish meal (9%) with titanium oxide (0.30%) as the digestibility marker. Diet 1 (NC, negative control), as the basal diet, contained no antibiotics and no supplemental prebiotics or β-glucan. Diet 2 (PC, positive control), contained an antibiotic premix (Lincomix-44 at 0.10%) in the basal diet at the expense of cornstarch. Diets 3, 5 and 6 contained 0.75% of the three test prebiotics of retrograded cornstarch (Diet 3), Fibersol-2 (Diet 5, a modified digestion-resistant maltodextrin) and inulin (Diet 6), and the viscous soluble fiber oat β-glucan (Diet 4), respectively, at the expense of cornstarch. A total of 144 Yorkshire pigs, at the age of 21 days (d) and an average body weight (BW) of 5.5 kg, were allocated to 12 floor pens with 3 barrows and 3 gilts per pen, and fed one of the 6 diets for 21 d in 2 study blocks according to a completely randomized block design. Initial and final pig BW, average daily gain (ADG), average daily feed intake (ADFI), representative pig plasma urea concentration as well as the apparent total tract DM and lactose digestibility during d 8-15 were measured. Analyses of variances, Dunnett’s and Tukey’s tests were conducted on the endpoints by using the SAS mixed model. There were no differences (P > 0.05) in ADG, ADFI, feed to gain ratio, plasma urea concentration, the apparent total tract apparent DM and lactose digestibility and the predicted whole-gut lactase digestive capacity among the diets, as examined by the Tukey’s test. There were no differences (P > 0.05) in these endpoints between each of the four treatment diets and the NC or the PC diet as examined by the Dunnett’s test. The total tract lactose digestibility was determined to be at 100%. The predicted whole-gut lactase digestive capacity was about eight times of the daily lactose intake when dietary lactose contents were supplemented at 10 - 12% (as-fed basis). In conclusion, dietary supplementation (at 0.75%) of the prebiotics and the oat β-glucan did not significantly affect the major growth performance endpoints, whole-body protein utilization status as well as the apparent total tract DM and lactose digestibility in the weanling pigs fed the corn and SBM-based diets. The promoting effect for growth and nitrogen utilization associated with dietary supplementation of lactose is due to the fact that lactose is a completely and rapidly digestible sugar rather than acting as an effective prebiotic in weanling pig nutrition.

The gas-particle flow with multiple dispersed solid phases is associated with a complicated multiphase flow dynamics. In this paper, a unified algorithm is proposed for the gas-particle multiphase flow. The gas-kinetic scheme (GKS) is used to simulate the gas phase and the multiscale unified gas-kinetic wave-particle (UGKWP) method is developed for the multiple dispersed solid particle phase. For each disperse solid particle phase, the decomposition of deterministic wave and statistic particle in UGKWP is based on the local cell's Knudsen number. The method for solid particle phase can become the Eulerian fluid approach at the small cell's Knudsen number and the Lagrangian particle approach at the large cell's Knudsen number. This becomes an optimized algorithm for simulating dispersed particle phases with a large variation of Knudsen numbers due to different physical properties of the individual particle phase, such as the particle diameter, material density, etc. The GKS-UGKWP method for gas-particle flow unifies the Eulerian-Eulerian and Eulerian-Lagrangian methods. The particle and wave decompositions for the solid particle phase and their coupled evolution in UGKWP come from the consideration to balance the physical accuracy and numerical efficiency. Two cases of a gas-solid fluidization system, i.e. one circulating fluidized bed and one turbulent fluidized bed, are simulated. The typical flow structures of the fluidized particles are captured, and the time-averaged variables of the flow field agree well with the experimental measurements. In addition, the shock particle-bed interaction is studied by the proposed method, which validates the algorithm for the polydisperse gas-particle system in the highly compressible case, where the dynamic evolution process of the particle cloud is investigated. [ABSTRACT FROM AUTHOR]

Introduction: Aneurysmal bone cysts (ABCs) are a rare benign bone lesion, which are divided into primary and secondary categories, and occur mainly in the vertebra and the long tubular bones. Primary ABCs in the nasal cavity and the sinuses are rare. Case presentation: We reported on a one-year-old boy who suffered from progressive nasal obstruction and intermittent nosebleeds over a period of approximately 1 month. The patient had no history of trauma or surgery. Physical examination showed a red tumor in his right nasal cavity. A magnetic resonance imaging scan showed a multicystic lesion arising from the ethmoid sinus. The lesion was resected under a nasal endoscope without any complications. Histological evaluation confirmed that the lesion was an aneurysmal bone cyst. Because an osteoma was found during the surgery on the cyst, the lesion was considered secondary clinically. However, fluorescence in situ hybridization testing showed a rearrangement of the USP6 (ubiquitin-specific protease 6) oncogene on chromosome 17. No recurrence was observed after 1 year. Conclusion: An ABC of the nasal cavity and sinuses in such a young child is very rare and needs to be further analyzed according to postoperative pathology and combined with a genetic examination to make a diagnosis. Endoscopic sinus surgery is an effective method of treatment for this kind of disease. [ABSTRACT FROM AUTHOR]