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Dong-Mei Cai,1,&ast; Fan-Biao Mei,1,&ast; Chao-Jun Zhang,1 San-Chun An,1 Rui-Bo Lv,1 Guan-Hua Ren,1 Chan-Chan Xiao,1 Long Long,1,2 Tian-Ren Huang,1,2 Wei Deng1,2 1Department of Experimental Research, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, 530021, People’s Republic of China; 2Guangxi Cancer Molecular Medicine Engineering Research Center, Nanning, Guangxi, 530021, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei Deng; Tianren Huang, Department of Experimental Research, Guangxi Medical University Cancer Hospital, No. 71, Hedi Road, Nanning, Guangxi, 530021, People’s Republic of China, Email dengwei@gxmu.edu.cn; tianrenhuang@sina.comBackground: Microcystin-LR (MC-LR) and hepatitis B virus (HBV) are associated with hepatocellular carcinoma (HCC). However, the concentrations of MC-LR in drinking water and the synergistic effect of MC-LR and HBV on hepatocellular carcinogenesis through their disturbance of redox balance have not been fully elucidated.Methods: We measured the MC-LR concentrations in 168 drinking water samples of areas with a high incidence of HCC. The relationships between MC-LR and both redox status and liver diseases in 177 local residents were analyzed. The hepatoma cell line HepG2 transfected with C-terminal truncated hepatitis B virus X gene (Ct-HBX) were treated with MC-LR. Reactive oxygen species (ROS), superoxide dismutase (SOD), glutathione (GSH) and malondialdehyde (MDA) were measured. Cell proliferation, migration, invasion, and apoptosis were assessed with cell activity assays, scratch and transwell assays, and flow cytometry, respectively. The mRNA and protein expression-related redox status genes were analyzed with qPCR and Western blotting.Results: The average concentration of MC-LR in well water, river water and reservoir water were 57.55 ng/L, 76.74 ng/L and 132.86 ng/L respectively, and the differences were statistically significant (P < 0.05). The MC-LR levels in drinking water were correlated with liver health status, including hepatitis, clonorchiasis, glutamic pyruvic transaminase abnormalities and hepatitis B surface antigen carriage (all P values < 0.05). The serum MDA increased in subjects who drank reservoir water and were infected with HBV (P < 0.05). In the cell experiment, ROS increased when Ct-HBX-transfected HepG2 cells were treated with MC-LR, followed by a decrease in SOD and GSH and an increase in MDA. MC-LR combined with Ct-HBX promoted the proliferation, migration and invasion of HepG2 cells, upregulated the mRNA and protein expression of MAOA gene, and downregulated UCP2 and GPX1 genes.Conclusion: MC-LR and HBV may synergistically affect redox status and play an important role in hepatocarcinoma genesis.Keywords: hepatocellular carcinoma, microcystins-LR, hepatitis B virus X gene, redox balance

Residential care services are under increasing pressure to lower service provision costs while maintaining quality of care. Using a translog cost function, this paper examines the relationship between cost, quality and output in England's learning disability (LD) residential care sector. It finds genuine but diminishing economies of scale in LD residential care services vis-à-vis output (i.e., care weeks). However, some variation exists: higher-quality LD residential care homes appear to have larger economies of scale than lower-quality ones. Supplementary regression analysis, examining quality-size, further finds quality (a) is negatively associated with LD care homes of six or fewer beds; (b) shows no association with homes of more than six beds. These findings enhance residential care literature and raise the possibility that, by promoting the establishment of larger high-quality care homes, cost savings may be achieved without sacrificing quality., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Lenvatinib is a multitargeted tyrosine kinase inhibitor capable of promoting apoptosis, suppressing angiogenesis, inhibiting tumor cell proliferation, and modulating the immune response. In multiple cancer types, lenvatinib has presented manageable safety and is currently approved as an effective first-line therapy. However, with the gradual increase in lenvatinib application, the inevitable progression of resistance to lenvatinib is becoming more prevalent. A series of recent researches have reported the mechanisms underlying the development of lenvatinib resistance in tumor therapy, which are related to the regulation of cell death or proliferation, histological transformation, metabolism, transport processes, and epigenetics. In this review, we aim to outline recent discoveries achieved in terms of the mechanisms and potential predictive biomarkers of lenvatinib resistance as well as to summarize untapped approaches available for improving the therapeutic efficacy of lenvatinib in patients with various types of cancers., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Type 2 diabetes mellitus (T2DM) is a metabolic disease with increasing prevalence and mortality year by year. The purpose of this study was to explore new therapeutic targets and candidate drugs for multitargets by single-cell RNA expression profile analysis, network pharmacology, and molecular docking. Single-cell RNA expression profiling of islet β cell samples between T2DM patients and nondiabetic controls was conducted to identify important subpopulations and the marker genes. The potential therapeutic targets of T2DM were identified by the overlap analysis of insulin-related genes and diabetes-related genes, the construction of protein-protein interaction network, and the molecular complex detection (MCODE) algorithm. The network distance method was employed to determine the potential drugs of the target. Molecular docking and molecular dynamic simulations were carried out using AutoDock Vina and Gromacs2019, respectively. Eleven cell clusters were identified by single-cell RNA sequencing (scRNA-seq) data, and three of them (C2, C8, and C10) showed significant differences between T2DM samples and normal samples. Eight genes from differential cell clusters were found from differential cell clusters to be associated with insulin activity and T2DM. The MCODE algorithm built six key subnetworks, with five of them correlating with inflammatory pathways and immune cell infiltration. Importantly, CCR5 was a gene within the key subnetworks and was differentially expressed between normal samples and T2DM samples, with the highest area under the ROC curve (AUC) of 82.5% for the diagnosis model. A total of 49 CCR5-related genes were screened, and DB05494 was identified as the most potential drug with the shortest distance to CCR5-related genes. Molecular docking illustrated that DB05494 stably bound with CCR5 (-8.0 kcal/mol) through multiple hydrogen bonds (LYS26, TYR37, TYR89, CYS178, and GLN280) and hydrophobic bonds (TRP86, PHE112, ILE198, TRP248, and TYR251). This study identified CCR5 as a potential therapeutic target and screened DB05494 as a potential drug for T2DM treatment., Competing Interests: No potential conflicts of interest relevant to this article were reported., (Copyright © 2022 Wan Zhou et al.)

The progressive destruction of condylar cartilage is a hallmark of the temporomandibular joint (TMJ) osteoarthritis (OA); however, its mechanism is incompletely understood. Here, we show that Kindlin-2, a key focal adhesion protein, is strongly detected in cells of mandibular condylar cartilage in mice. We find that genetic ablation of Kindlin-2 in aggrecan-expressing condylar chondrocytes induces multiple spontaneous osteoarthritic lesions, including progressive cartilage loss and deformation, surface fissures, and ectopic cartilage and bone formation in TMJ. Kindlin-2 loss significantly downregulates the expression of aggrecan, Col2a1 and Proteoglycan 4 (Prg4), all anabolic extracellular matrix proteins, and promotes catabolic metabolism in TMJ cartilage by inducing expression of Runx2 and Mmp13 in condylar chondrocytes. Kindlin-2 loss decreases TMJ chondrocyte proliferation in condylar cartilages. Furthermore, Kindlin-2 loss promotes the release of cytochrome c as well as caspase 3 activation, and accelerates chondrocyte apoptosis in vitro and TMJ. Collectively, these findings reveal a crucial role of Kindlin-2 in condylar chondrocytes to maintain TMJ homeostasis., (© 2022. The Author(s).)

Objective: Nasal bone fractures are the most common facial bone fractures. However, there is limited literature on the etiology of these fractures, particularly distribution across sports and other recreational activities., Methods: The Nationwide Electronic Injury Surveillance System (NEISS) national injury database was queried for emergency department visits involving the diagnosis of nasal or nose fractures associated with sports and recreation activities over the most recent 10 year span available. Demographic, disposition, and weighted incidence were analyzed., Results: Total incidence of nasal fractures across 10 years was 158 979. The mean age of nasal bone fractures was 20.4 years old. Nasal fractures were more common in males (74.6%) and white patients (54.1%). National estimated incidence of nasal fractures decreased from 21 028 in 2009 to 11 108 in 2018, a reduction of 47.2%. The most common causes among all patients were basketball (23.2%), baseball (17.1%), softball (9.8%), soccer (7.4%), and football (7%). In pediatric patients, the most common cause was baseball (25.1%). The majority (98.1%) of patients were discharged from the emergency department, while 0.9% of patients were admitted., Conclusion: The most common recreational causes of nasal fractures are sports, with the most common being non-contact sports like basketball and baseball. However, the incidence of nasal bone fractures due to recreational causes nationwide has decreased significantly over the past 10 years. This may reflect improved safety protocols among athletes.

Plant hormone abscisic acid (ABA) plays an indispensable role in the control of leaf senescence, during which ABA signaling depends on its biosynthesis. Nevertheless, the role of ABA transport in leaf senescence remains unknown. Here, we identified two novel RING-box protein-encoding genes UBIQUITIN LIGASE of SENESCENCE 1 and 2 (ULS1 and ULS2) involved in leaf senescence. Lack of ULS1 and ULS2 accelerates leaf senescence, which is specifically promoted by ABA treatment. Furthermore, the expression of senescence-related genes is significantly affected in mature leaves of uls1/uls2 double mutant (versus wild type (WT)) in an ABA-dependent manner, and the ABA content is substantially increased. ULS1 and ULS2 are mainly expressed in the guard cells and aging leaves, and the expression is induced by ABA. Further RNA-seq and quantitative proteomics of ubiquitination reveal that ABA transporter ABCG40 is highly expressed in uls1/uls2 mutant versus WT, though it is not the direct target of ULS1/2. Finally, we show that the acceleration of leaf senescence, the increase of leaf ABA content, and the promotion of stomatal closure in uls1/usl2 mutant are suppressed by abcg40 loss-of-function mutation. These results indicate that ULS1 and ULS2 function in feedback inhibition of ABCG40-dependent ABA transport during ABA-induced leaf senescence and stomatal closure., (© 2022 Institute of Botany, Chinese Academy of Sciences.)

Objective: This case report aims to increase awareness of the diagnosis of laryngeal cleft in adult patients and discuss treatment options., Methods: Case report and review of the literature., Results: We present a case of a 56-year-old male referred for hoarseness and chronic cough that was discovered to have a type 2 laryngeal cleft. He had chronic aspiration, recurrent pneumonia, and a hoarse voice for his entire life. In contrast to most described cases in adults, this patient was successfully treated with an endoscopic approach using absorbable suture., Conclusion: Laryngeal clefts are uncommon and almost always detected in childhood, making adult laryngeal clefts extremely rare. Endoscopic repair is a feasible and successful treatment option in these cases., (Copyright © 2020 The Voice Foundation. Published by Elsevier Inc. All rights reserved.)

Abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) are one of the main causes of the development of diabetic atherosclerotic process. The aim of our study was to assess the role of RBP4 in the proliferation and migration of VSMCs and the inhibitory effect of vitamin D on the mechanisms. In an in vivo experiment, rats were randomly classified into 6 groups: the control group, diabetic rats, diabetic atherosclerotic rats (diabetic rats intraperitoneally injected with RBP4), diabetic atherosclerotic rats treated with 0.075  μ g kg -1  d -1 vitamin D, 0.15  μ g kg -1  d -1 vitamin D and 0.3  μ g kg -1  d -1 vitamin D. We found that the levels of JAK2, STAT3, cylinD1, and Bcl-2 were increased in diabetic atherosclerotic rats, and these increases were improved after vitamin D supplementation. Furthermore, to investigate the underlying molecular mechanisms, cells were cultured with glucose in the presence of RBP4 and the absence of RBP4, respectively, and vitamin D of different concentrations and different intervention times was simultaneously adopted. The proliferation and migration of VSMCs was enhanced and the levels of JAK2, STAT3, cyclinD1, and Bcl-2 were increased in the cells transfected with RBP4 overexpression plasmid. Moreover, vitamin D supplementation was detected to lower the expressions of JAK2, STAT3, cyclinD1, and Bcl-2 and inhibit the abnormal proliferation of VSMCs caused by the RBP4/JAK2/STAT3 signaling pathway. RBP4 can promote the proliferation and migration of VSMCs and contributes to the development of diabetic macroangiopathy via regulating the JAK2/STAT3 signaling pathway. This mechanism of RBP4 can be inhibited by vitamin D supplementation., Competing Interests: No potential conflicts of interest relevant to this article were reported., (Copyright © 2022 Wan Zhou et al.)

Objectives: Changes in airflow dynamics after nasal surgery may have implications on voice quality. Multiple studies have evaluated the impact of nasal surgery on voice using heterogeneous outcome measures. We aim to systematically review the impact of nasal surgery on voice quality., Methods: Our study design was a systematic review with meta-analyses. A literature search of PubMed, Ovid, Cochrane from 1997 to 2017 was performed. Inclusion criteria included English language studies containing original data on nasal surgery and voice. Two investigators independently reviewed all manuscripts and performed a comprehensive quality assessment. Meta-analysis was completed on quantitative voice measurements., Results: Of 463 identified, 19 studies with 692 patients fulfilled eligibility. Nasal surgeries performed included endoscopic sinus surgery (11/20), septoplasty (11/20), rhinoplasty (2/20), and turbinate reduction (2/20). Voice outcomes measured included nasalance (8/20), fundamental frequency (11/20), jitter (10/20), shimmer (10/20), harmonic to noise ratio (HRN) (8/20), formants (5/20), and voice handicap index (VHI) (4/20). Voice examinations were assessed preoperatively and 1 to 30 months postoperatively. Meta-analysis revealed statistically significant changes in nasalance, ( P  < .01) 1 month postoperatively; there was no significant difference in nasalance at 6 months postoperatively. All other variables analyzed revealed no statistically significant differences. Five of nine studies showed majority of patients did not notice subjective change in voice after surgery, but with high heterogeneity of measurements., Conclusions: There may be a short-term increase in nasalance that resolves at longer follow-up, but there seem to be no other objective changes in voice. There may be subjective changes after surgery, but require further study to evaluate.

Objectives: To estimate the incidence of emergency department visits for pediatric ear foreign bodies. To identify the most common items and their trends., Methods: The Nationwide Electronic Injury Surveillance System (NEISS) was queried for emergency department visits involving the diagnosis of foreign bodies in the ear including pinna and canal in children over the most recent 10-year span available. National incidence estimates and demographic data were extracted from the same database., Results: Ear foreign bodies in children made up an estimated total 446,819 ED visits nationwide over the past 10 years. The mean age was 7.2 ± 4.3 years old. The majority (55.6%, n = 248,531) of cases were female. The most common class of objects found was jewelry, primarily embedded earrings and beads, accounting for 55.5% visits, followed by paper products at 7.1%, pens and pencils at 4.1%, desk supplies (erasers) at 3.7%, BBs or pellets at 3.5%, and earplugs and earphones at 3%. Females were significantly more likely to have jewelry foreign bodies, and males were significantly more likely to have foreign bodies from all other categories other than first-aid supplies., Conclusion: Foreign bodies of the ear are a common reason for emergency department visits in children, primarily jewelry, paper products, and desk supplies. Recognition of commonly encountered objects can aid in both speedier recognition of unknown objects, as well as guide patient counseling., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objective: To investigate the expression and clinical significance of LRFN4 in colorectal cancer. Methods: A total of 210 cases of colorectal cancer tissues and 228 cases of corresponding surgical margin tissues were collected. Immunohistochemistry was employed to evaluate the expression of LRFN4 in colorectal cancer.The correlation between LRFN4 expression and clinicopathological features of colorectal cancer as well as patient outcome were analyzed. Results: The positive rate of LRFN4 in colorectal cancer and in non-cancer was 55.24%(116/210), and 37.28% (85/228) , respectively.The expression of LRFN4 in colorectal cancer tissues was higher than that in non-cancer tissues(χ(2)=14.196, P <0.001). High expression of LRFN4 was significantly correlated with tumor location(χ(2)=4.133, P =0.042), T staging(χ(2)=6.494, P =0.039), N staging(χ(2)=11.715, P =0.008), TNM staging(χ(2)=13.398, P =0.004), CEA (χ(2)=6.017, P =0.049), but without gender, age, degree of differentiation, M staging( P >0.05).The Kaplan-Meier survival curves indicated that high LRFN4 expression was associated with good survival ( P <0.05). In addition, Cox proportional hazards model showed that the high expression of LRFN4( HR =0.585, P =0.018)was an independent risk factor for prognosis in patients with colorectal cancer. Conclusions: The expression of LRFN4 is up-regulated in colorectal cancer, which is significantly correlated with the clinicopathological features and prognosis. High expression of LRFN4 reduced the risk of death in patients with colorectal cancer.

Objective: Racial disparities have been well characterized and African American (AA) patients have 30% lower 5-year survival rates than European Americans (EAs) for head and neck squamous carcinoma (HNSCC). This poorer survival can be attributed to a myriad of different factors. The purpose of this study was to characterize AA-EA similarities and differences in sociodemographic, lifestyle, clinical, and psychosocial characteristics in HNSCC patients near the time of surgery., Methods: Setting: Single tertiary care center. Participants: Thirty-nine newly diagnosed, untreated HNSCC patients ( n  = 24 EAs, n  = 15 AAs) who were to undergo surgery were recruited. Study Design: Cross-sectional study Sociodemographic, lifestyle factors, and disease factors (cancer site, AJCC clinical and pathologic stage, and HPV status)were assessed. Risk factors, leisure time, quality of life and social support were also assessed using validated questionnaires. Exposures: EA and AA patients were similar in the majority of sociodemographic factors assessed. AAs had a higher trend toward pathologically later stage disease compared to EAs and significantly increased time to treatment., Results: EA and AA patients were similar in the majority of sociodemographic factors assessed. AAs had a higher trend toward pathologically later stage disease compared to EAs. AAs also had significantly increased time to treatment ( P  = 0.05). The majority of AA patients (62%) had later stage pathologic disease. AA were less likely to complete high school or college ( P  = 0.01) than their EA counterparts. Additionally, AAs were more likely to report having a gap in health insurance during the past decade (37% vs . 15%)., Conclusions: This preliminary study demonstrates a similar profile of demographics, clinical and psychosocial characteristics preoperatively for AAs and EAs. Key differences were AAs tending to have later pathologic stage disease, educational status, delays in treatment initiation, and gaps in health insurance., Competing Interests: None., (© 2020 Chinese Medical Association. Production and hosting by Elsevier B.V. on behalf of KeAi Communications Co., Ltd.)

Objectives: To examine the national rates of complications, readmission, reoperation, death and length of hospital stay after laryngectomy. To explore the risks of neck dissection with laryngectomy using outcomes., Methods: The American College of Surgeons National Quality Improvement Program (ACS-NSQIP) database was reviewed retrospectively. The database was analyzed for patients undergoing laryngectomy with and without neck dissection. Demographic, perioperative complication, reoperation, readmission, and death variables were analyzed., Results: 754 patients who underwent total laryngectomy during this time were found. Demographic analysis showed average age was 63 years old, 566 (75.1%) were white, and 598 (79.3%) were male. Of these patients, 520 (69.0%) included a neck dissection while 234 (31.0%) did not. When comparing patients who received a neck dissection to those who did not, there were no significant differences in median length of hospital stay (12.5 days w/ vs. 13.3 days w/o, P  = 0.99), rates of complication (40% w/ vs. 35% w/o, P  = 0.23), reoperation (13.5% w/ vs. 14% w/o, P  = 0.81), readmission (14% w/ vs. 18% w/o, P  = 0.27), and death (1.3% w/ vs. 1.3% w/o, P  > 0.99). Furthermore, neck dissection did not increase the risk of complication ( P  = 0.23), readmission ( P  = 0.27), reoperation ( P  = 0.81), death ( P  = 0.94), or lengthened hospital stay ( P  = 0.38)., Conclusions: Concurrent neck dissection does not increase postoperative morbidity or mortality in patients undergoing total laryngectomies. These results may help physicians make decisions regarding concurrent neck dissection with total laryngectomy., Competing Interests: None., (© 2019 The Authors.)

Coal-based porous materials for supercapacitors were successfully prepared using Taixi anthracite (TXA) by multi-stage activation. The characterization and electrochemical tests of activated carbons (ACs) prepared in different stages demonstrated that the AC from the third-stage activation (AC III ) shows good porous structures and excellent electrochemical performances. AC III exhibited a fine specific capacitance of 199 F g -1 at a current density of 1 A g -1 in the three-electrode system, with 6 mol L -1 KOH as the electrolyte. The specific capacitance of AC III remained 190 F g -1 even despite increasing the current density to 5 A g -1 , indicating a good rate of electrochemical performance. Moreover, its specific capacitance remained at 98.1% of the initial value after 5000 galvanostatic charge-discharge (GCD) cycle tests at a current density of 1 A g -1 , suggesting that the AC III has excellent cycle performance as electrode materials for supercapacitors. This study provides a promising approach for fabricating high performance electrode materials from high-rank coals, which could facilitate efficient and clean utilization of high-rank coals.

Objectives: Hydrogen sulfide (H 2 S) attenuates ischemia-reperfusion injury (IRI) in different organs. However, its mechanism of action in renal IRI remains unclear. The present study investigated the hypothesis that H 2 S attenuates renal IRI via the induction of heat shock proteins (HSPs)., Materials and Methods: Adult Wistar rats were subjected to unilateral renal ischemia for 45 min followed by reperfusion for 6 hr. One group of rats underwent I/R without treatment, one group was administered 150 μmol/l sodium hydrosulfide (NaHS) prior to I/R, one group was injected with 100 mg/kg quercetin (an HSP inhibitor) intraperitoneally prior to I/R, and another group received quercetin prior to I/R and treatment with NaHS following I/R. Two other groups underwent a sham operation and one of them received 150 μmol/l NaHS following the sham operation whereas the other received no treatment. Renal function and histological changes were compared and relevant indices of oxidative stress, apoptosis, and inflammation were examined., Results: IRI increased serum creatinine and blood urea nitrogen concentrations, promoted lipid peroxidation by elevating malondialdehyde levels, suppressed superoxide dismutase activity, stimulated inflammation by inducing NF-kB, IL-2, and TLR-4 expression, and increased renal apoptosis. Levels of HSP 70, heme-oxygenase-1 (HO-1) and HSP 27 were increased following IRI and reversed following H 2 S treatment. H 2 S attenuated changes observed in pathology, lipid peroxidation, inflammation, and apoptosis following IRI. The administration of quercetin reversed all protective effects of H 2 S., Conclusion: The present study indicated that H 2 S protected renal tissue against IRI induced lipid peroxidation, inflammation, and apoptosis, which may be attributed to the upregulation of HSP 70, HO-1, and HSP 27., Competing Interests: All authors declare no conflicts of interest.

The Yongjiang river is a large, shallow, hyper-trophic, freshwater river in Guangxi, China. To investigate the presence of microcystin-RR, microcystin-LR, and microcystin-YR (MC-RR, MC-LR, and MC-YR) in the Yongjiang river and describe their correlation with environmental factors, as well as, assess health risk using Monte Carlo simulation, 90 water samples were collected at three sample points from March to December 2017. Results showed that during the monitoring period, total concentrations of MC-RR (TMC-RR), MC-YR (TMC-YR), and MC-LR (TMC-LR) varied from 0.0224 to 0.3783 μg/L, 0.0329 to 0.1433 μg/L, and 0.0341 to 0.2663 μg/L, respectively. Total phosphorus (TP) content appeared to be related to TMC-LR and the total concentrations of microcystins (TMCs), while pH and total nitrogen (TN)/TP ratio appeared to be related to TMC-RR and TMC-YR, respectively. Using the professional health risk assessment software @Risk7.5, the risks of dietary intake of microcystins (MCs), including the carcinogenic risk and non-carcinogenic risk, were evaluated. It was found that the carcinogenic risk of MC-RR from drinking water was higher than MC-LR and MC-YR, and the presence of MCs would lead to high potential health risks, especially in children. The carcinogenic risk of MC-RR to children was >1 × 10 -4 , the maximum allowance level recommended by the US Environmental Protection Agency; as for adults, it was >5 × 10 -5 , the maximum allowance level recommended by the International Commission on Radiological Protection. The non-carcinogenic hazard index (HI) of MC-RR, MC-YR, and MC-LR increased successively, indicating that MC-LR was more hazardous to human health than MC-YR and MC-RR, but its HI was <1. This suggests that MCs pose less risk to health. However, it is necessary to strengthen the protection and monitoring of drinking water source for effective control of water pollution and safeguarding of human health., Competing Interests: The authors declare that they have no competing interests.

Background: Chronic rhinosinusitis (CRS) is a prevalent illness in the United States that accounts for 18-22 million physician visits annually. The American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) has defined diagnostic criteria, but a recent study demonstrated that nearly all patients diagnosed by nonspecialists did not meet these criteria. In this study we aimed to evaluate the diagnostic rate of CRS by primary care physicians and otolaryngologists., Methods: We retrospectively reviewed a random sample of adult patients diagnosed with CRS in 2016, based on ICD-10 codes from primary care and otolaryngology departments. Patients with previous CRS diagnosis, previous sinus surgery, and related comorbidities were excluded., Results: A total of 502 patients with a new CRS diagnosis were analyzed (308 from primary care, 194 from otolaryngology). The percentage of diagnoses meeting the criteria was significantly higher from otolaryngology (28.9% vs 0.97%, p < 0.0001), but was low in both cohorts. Symptom duration <12 weeks was higher in primary care (81.6% vs 53.6%, p < 0.0001), as was lack of evidence of inflammation (97.4% vs 50.0%, p < 0.0001). Having <2 of the required symptoms was significantly higher in otolaryngology (63.8% vs 50.8%, p = 0.013). The most commonly unevaluated symptom was decreased sense of smell (97.7% in primary care, 69.1% in otolaryngology encounters)., Conclusion: CRS diagnoses commonly do not meet the diagnostic criteria outlined by the AAO-HNS in both primary care and otolaryngology. As a specialty, we should aim to improve our adherence to the guidelines and educate our primary care colleagues to better identify patients with CRS and initiate appropriate treatment., (© 2018 ARS-AAOA, LLC.)

Although several studies indicated an association between diurnal temperature range (DTR) and mortality, the results about modifiers are inconsistent, and few studies were conducted in developing inland country. This study aims to evaluate the effects of DTR on cause-specific mortality and whether season, gender, or age might modify any association in Hefei city, China, during 2007-2016. Quasi-Poisson generalized linear regression models combined with a distributed lag non-linear model (DLNM) were applied to evaluate the relationships between DTR and non-accidental, cardiovascular, and respiratory mortality. We observed a J-shaped relationship between DTR and cause-specific mortality. With a DTR of 8.3 °C as the reference, the cumulative effects of extremely high DTR were significantly higher for all types of mortality than effects of lower or moderate DTR in full year. When stratified by season, extremely high DTR in spring had a greater impact on all cause-specific mortality than other three seasons. Male and the elderly (≥ 65 years) were consistently more susceptible to extremely high DTR effect than female and the youth (< 65 years) for non-accidental and cardiovascular mortality. To the contrary, female and the youth were more susceptible to extremely high DTR effect than male and the elderly for respiratory morality. The study suggests that extremely high DTR is a potential trigger for non-accidental mortality in Hefei city, China. Our findings also highlight the importance of protecting susceptible groups from extremely high DTR especially in the spring.

Background/objective: The etiology and risk factors for angioedema remain poorly understood with causative triggers often going undiagnosed despite repeated reactions. The purpose of this study was to determine the relationship between inhalant allergen sensitization and angioedema., Methods: A retrospective review of patients who had in vitro inhalant allergy testing from 2006 to 2010 was performed. Patients with a diagnosis of angioedema who underwent inhalant allergy testing were identified. Analyses for co-morbidities, class of sensitization, seasonal timing of angioedema, and concurrent use of known hypertensive medications that can cause angioedema were performed., Results: There were 1000 patients who underwent inhalant allergy testing and qualified for the study. 37/1000 had at least one episode of angioedema and of these patients, 34 had positive inhalant sensitization testing results. Multivariate regression models showed overall sensitization status, seasonal allergen and epidermal/mite sensitization as independent risk factors (p<0.001, p=0.005, p=0.025 respectively) when controlling for ACE inhibitor use and other covariates. Tree, and epidermal/mite sensitizations were independent risk factors for angioedema in mono-sensitized subject analysis (p=0.028, p=0.029, respectively)., Conclusion: Both seasonal and perennial allergen sensitizations are independent risk factors for the development of angioedema. In patients with angioedema and an unknown trigger, inhalant allergen sensitization should be considered as a potential contributing factor to the development of angioedema., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: To investigate the association between air pollution and upper respiratory tract infection (URTI) in children aged 0-14 years in Hefei, China in 2014-2015., Study Design: An ecological method (i.e. generalised additive model [GAM]) was used to explore the effects of air pollutants on paediatric hospital outpatients with URTI., Methods: GAM was used to evaluate the lag effects (including lag0 to lag6, lag01 and lag06) between daily changes in particulate matter (PM 10 ), fine particulate matter (PM 2.5 ), sulphur dioxide (SO 2 ), nitrogen dioxide (NO 2 ), ozone (O 3 ) and carbon monoxide (CO) and the number of hospital outpatients with URTI in 2014-2015, after controlling for the confounding effects of long-term trends, seasonality, day of the week, public holidays and meteorological factors., Results: PM 10 , PM 2.5 , SO 2 , NO 2 and CO in the single-pollutant models had significant positive effects on the number of paediatric hospital outpatients with URTI. It was found that per 10 μg/m 3 increasing in concentrations of PM 10 at lag3, PM 2.5 , SO 2 , NO 2 and CO at lag06 were associated with an increase of Excess risk (ER) with 0.15% (95% CI: 0.07%∼0.23%), 0.38% (95% CI: 0.17%∼0.60%), 2.92% (95% CI: 1.88%∼3.97%), 4.47% (95% CI: 3.69%∼5.25%) and 0.05% (95% CI: 0.02%∼0.08%), respectively. Only NO 2 remained significantly positively associated with the number of hospital outpatients with URTI in the full-pollutant models, and ERs were 4.72% (95% CI = 3.76%-5.69%) and 4.70% (95% CI = 3.76%-5.65%) per 10 μg/m 3 increase in NO 2 in Model 1 (including PM10, SO 2 , NO 2 , O 3 and CO) and Model 2 (including PM 2.5 , SO 2 , NO 2 , O 3 and CO), respectively., Conclusion: This study showed that short-term exposure to air pollution was associated with increased risk of URTI among paediatric hospital outpatients aged 0-14 years in Hefei. NO 2 was the major air pollutant affecting the daily number of paediatric hospital outpatients with URTI., (Copyright © 2017 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.)

The aim of the present study was to evaluate whether morpholin-4-ium 4 methoxyphenyl (morpholino) phosphonodithioate (GYY4137) exhibits a protective effect on ipsilateral testicular injury in experimentally varicocele (VC)-induced rats. A total of 48 rats were randomly divided into the following 6 groups (n=8 each): Group A (control group); group B (sham group); group C (VC group); group D (VC group administered 5 mg/kg/day GYY4137); group E (VC group administered 10 mg/kg/day GYY4137) and group F (VC group administered 20 mg/kg/day GYY4137). Indicators of oxidative stress, apoptosis and inflammation were measured to evaluate the effect of GYY4137 on ipsilateral testicular injury. Compared with groups A and B, rats in group C exhibited severe histological changes and an increase in oxidative stress, apoptosis and inflammation. By contrast, amelioration of testicular damage was evident in the group D, E and F that were treated with GYY4137. These results demonstrate that GYY4137 may be a promising therapy to treat VC as it alleviates oxidative stress, apoptosis and inflammation in experimentally VC-induced rats.

Background/aims: Accumulating evidences has indicated that aberrant expression of long non-coding RNAs (lncRNAs) is tightly associated with the progression of ischemia-reperfusion injury (IRI). Previous studies have reported that lncRNA MALAT1 regulates cell apoptosis and proliferation in myocardial and cerebral IRI. However, the underlying mechanism of MALAT1 in testicular IRI has not been elucidated., Methods: The levels of MALAT1, some related proteins and apoptosis in the testicular tissues were determined by quantitative real-time PCR, HE staining, immunohistochemistry, western blot and TUNEL assays. Relative expression of MALAT1, miR-214 and related proteins in cells were measured by western blot and quantitative real-time PCR. Cell viability and apoptosis were examined using MTT assay and flow cytometry., Results: In the present study, we found that MALAT1 was up-regulated in animal samples and GC-1 cells. The expression level of MALAT1 was positively related to cell apoptosis and negatively correlated with cell proliferation as testicular IRI progressed. In gain and loss of function assays, we confirmed that MALAT1 promotes cell apoptosis and suppresses cell proliferation in vitro and in vivo. Furthermore, we found that MALAT1 negatively regulates expression of miR-214 and promotes TRPV4 expression at the post-transcriptional level. Consequently, we investigated the correlation between MALAT1 and miR-214 and identified miR-214 as a direct target of MALAT1. In addition, we found that TRPV4 acted as a target of miR-214. Over-expression of miR-214 efficiently abrogated the up-regulation of TRPV4 induced by MALAT1, suggesting that MALAT1 positively regulates the expression of TRPV4 by sponging miR-214., Conclusion: In sum, our study indicated that the lncRNA MALAT1 promotes cell apoptosis and suppresses cell proliferation in testicular IRI via miR-214 and TRPV4., (© 2018 The Author(s). Published by S. Karger AG, Basel.)

HBV quasispecies are closely related to the course and outcome of liver disease. However, whether the complexity and diversity of HBX quasispecies affects its integration in the liver cell and thereby enhances the resultant carcinogenesis is still not clear. 15 HCC patients were recruited; genomic DNA and HBV DNA were extracted from liver cancer tissue and serum respectively. The integrated HBX fragment in liver cancer tissue was amplified by Alu repeat sequence-polymerase chain reaction (Alu-PCR) and sequenced. The serum HBX gene was amplified by nested PCR and sequenced. Quasispecies complexity and diversity, phylogenetic characteristics, lymphocyte count and survival time between HBX-integrated and HBX-unintegrated patients were evaluated. Results showed that the integrated HBX fragment was detected in the tumor tissue of nine patients, and the integration rate was 60.00% (9/15). Compared with the HBX-unintegrated patients, the HBX-integrated patients had a higher quasispecies complexity ( P =0.028 and 0.004, at the nucleotide and amino acid levels, respectively). The HBX-integrated patients had a tendency of higher quasispecies diversity, lower lymphocyte count and the survival time. A total of 12 mutation sites were revealed in the HBX-integrated fragment after alignment with the reference sequence. In these, the HBX-integrated groups had significantly higher mutation frequencies at C1497T, A1630G, G1721A, A1762T/G1764A and A1774G. This study revealed influence factors of HBX integration both in virus and the host. The increased complexity and diversity of HBX quasispecies might destroy the host immune balance, and lead to HBX integration ultimately., Competing Interests: None., (IJCEP Copyright © 2017.)

Background: MicroRNAs (miRNAs) have emerged as gene expression regulators in the progression of ischemia-reperfusion injury (IRI). Accumulating evidences have indicated miR-29a play roles in myocardial and cerebral IRI. However, the role of miR-29a in testicular IRI has not been elucidated. Methods: Changes in expression of miR-29a and Transient Receptor Potential Vanilloid 4 (TRPV4) in animal samples and GC-1 spermatogenic cells were examined. The effects of miR-29a on spermatogenic cell apoptosis in testicular IRI were analyzed both in vitro and in vivo . Results: The expression of MiR-29a was negatively correlated with the expression of TRPV4 and significantly downregulated in animal samples and GC-1 cells as testicular IRI progressed. Further studies revealed TRPV4 as a downstream target of miR-29a. Inhibition of miR-29a expression increased the expression of TRPV4 and promoted spermatogenic cell apoptosis, whereas overexpression of miR-29a downregulated TRPV4 expression and suppressed spermatogenic cell apoptosis caused by testicular IRI in vitro and in vivo . Conclusion: Our results suggest that miR-29a suppresses apoptosis induced by testicular IRI by directly targeting TRPV4.

Accumulating evidences have indicated that aberrant expression of long non-coding RNAs (LncRNAs) is tightly associated with cancer development. Previous studies have reported that lncRNA XIST regulates tumor malignancies in several cancers. However, the underlying mechanism of XIST in prostate cancer remains unclear. In the current study, we found that XIST was down-regulated in prostate cancer specimens and cell lines. Low expression of XIST was correlated with poor prognosis and advanced tumor stage in prostate cancer patients. In gain and loss of function assays, we confirmed that XIST suppressed cellular proliferation and metastasis in prostate cancer both in vitro and in vivo . Furthermore, we found that XIST negatively regulates the expression of miR-23a and subsequently promotes RKIP expression at post-transcriptional level. Consequently, we investigated the correlation between XIST and miR-23a, and identified miR-23a as a direct target of XIST. In addition, over-expression of miR-23a efficiently abrogated the up-regulation of RKIP induced by XIST, suggesting that XIST positively regulates the expression of RKIP by competitively binding to miR-23a. Taken together, our study indicated that lncRNA XIST acts as a tumor suppressor in prostate cancer, and this regulatory effect of XIST will shed new light on epigenetic diagnostics and therapeutics in prostate cancer., Competing Interests: CONFLICTS OF INTEREST The authors declare no conflicts of interest.

In the current study, the hypothesis that testicular varicocelectomy improves spermatogenesis and attenuates apoptosis via the induction of heat shock protein 70 (Hsp70) in a rat model of varicocele was investigated. Adult male Wistar rats (n=75) were randomly divided into 5 groups of 15 each: Control, sham, varicocele, varicocelectomy, and varicocelectomy plus Quercetin. A total of 6 weeks after the varicocelectomy, the left testis of all rats was removed for subsequent examination. Histological changes were compared between the groups. The expression of Hsp70 and apoptosis‑associated indicators were evaluated based on immunohistochemical, western blot and mRNA expression analyses. Compared with the varicocele group, the varicocelectomy group exhibited a markedly reduced Bcl‑2‑associated X protein/B‑cell lymphoma 2 (Bax/Bcl‑2) ratio, and had a decreased expression of caspase‑9, cytochrome c (cyt c) and caspase‑3 through the intrinsic signal transduction pathways. Quercetin treatment inhibited the protective effects of varicocelectomy. The expression of Hsp70 was increased in the varicocele group which was further elevated by the varicocelectomy. These results indicated that varicocelectomy can reduce the Bax/Bcl‑2 ratio, and decrease the levels of caspase‑9, cyt c and caspase‑3 via the mitochondrial signal transduction pathway. Such protective effects on left testis spermatogenesis and against apoptosis may be due to the induction of Hsp70. The findings of the present study suggested that varicocelectomy has a clear advantage in protecting testicular function and ameliorating spermatogenic cells apoptosis.

Zinc finger protein 687 (ZNF687), identified as a C2H2 zinc finger protein, has been found to be mutated and upregulated in giant cell tumor of bone and acute myeloid leukemia, suggesting an oncogenic role for ZNF687 in cancer. However, the clinical significance and precise role of ZNF687 in cancer progression are largely unknown. Herein, we report that ZNF687 was markedly upregulated in hepatocellular carcinoma (HCC) cell lines and HCC tissues, and was significantly correlated with relapse-free survival in HCC. ZNF687 overexpression greatly enhanced HCC cell capability for tumorsphere formation, invasion and chemoresistance in vitro, whereas inhibiting ZNF687 reduced these capabilities and inhibited HCC cell tumorigenic capability in vivo. Importantly, extreme limiting dilution analysis revealed that even 1 × 10 2 ZNF687-transduced cells could form tumors in vivo, indicating that ZNF687 contributes to HCC recurrence. Moreover, we demonstrate that ZNF687 transcriptionally upregulated the expression of the pluripotency-associated factors BMI1, OCT4 and NANOG by directly targeting their promoters. Therefore, our results suggest that ZNF687 has a promoter role in regulating HCC progression, which provides a potential therapeutic target for HCC in humans.

Objective: This present study was to examine the prevalence and determinants of one-night-stand behavior among young men who have sex with men (YMSM). Methods: A total of 403 YMSM aged 16 to 25 were recruited through internet promotion, extending activity and HIV VCT in Wuhan. Data was gathered through anonymous questionnaire. Binary logistic regression was used to examine factors associated with one-night-stand behavior. Results: Of the 398 YMSM, 48.99 % (195/398) reported having had casual sex in the last 6 months. Of the ones having had casual sex, 34.29 % (60/175) and 28.65 % (49/171) reported using condoms consistently during anal or oral sexual contacts, respectively. These figures were lower than those of YMSM not having casual sexual contacts [with anal sex as 49.08 % (80/163) and oral sex as 38.85 % (61/157)]. 76.80 % (149/194) of the YMSM reported having had multiple sexual partners, with the figure higher than those without [33.15 % (60/181)] ( P <0.01). Results from the logistic regression analysis showed that the following factors seemed to be associated with casual sex activities among YMSM, including: often using internet, ( OR =4.89, 95 %CI : 1.90-12.54), taking illegal drugs ( OR =2.72, 95 %CI : 1.60-4.63). Conclusions: YMSM who had engaged in casual sex, practicing unprotected sex or having multiple sexual partners, were recognized as high risk population. Targeted intervention programs are needed to decrease the one-night-stand behavior. Internet intervention strategy seemed an important method to serve the purpose.

Introduction: Acute invasive fungal rhinosinusitis (AIFRS) is a potentially fatal infection, usually affecting immunocompromised patients. Isolated sphenoid sinus involvement is rare and has been reported in only a few cases. We discuss the clinical characteristics, histopathologic features, and differential diagnosis of AIFRS of the sphenoid sinus., Case Presentation: A 57-year-old man with a history of refractory non-Hodgkin lymphoma and neutropenia presented with a 1-week duration of left-sided headache and ipsilateral cheek paresthesia. Nasal endoscopy showed mucoid drainage from the sphenoethmoidal recess. Magnetic resonance imaging demonstrated left sphenoid mucosal thickening and enhancement along the adjacent skull base. The patient underwent endoscopic sinus surgery with extended sphenoidotomy and débridement. The lateral wall and recess of the left sphenoid sinus demonstrated pale mucosa and fungal debris. Pathologic analysis demonstrated necrotic tissue and fungal hyphae with angioinvasion. Microbiology studies isolated Aspergillus fumigatus. The right maxillary sinus contained a synchronous fungal ball, which was removed during surgery; there was no evidence of tissue necrosis or invasive fungus in the maxillary sinus. He was treated with long-term voriconazole therapy, and 6-month follow-up showed disease resolution., Discussion: AIFRS should be considered in the differential diagnosis of immunocompromised patients with nonspecific sinonasal symptoms. Usually, AIFRS is diffuse with multiple sinus involvement; however, isolated sphenoid AIFRS can occur. This is one of the few cases of AIFRS demonstrating isolated sphenoid involvement and is thought to be the first case showing a synchronous noninvasive fungal ball of another sinus cavity. Prompt recognition and surgical treatment may be curative and lifesaving.

Background: Tisp40, a transcription factor of the CREB/CREM family, is involved in cell proliferation, differentiation and other biological functions, but its role in renal tubulointerstitial fibrosis is unknown., Methods: In our study, we investigated the effects of Tisp40 on extracellular matrix (ECM) accumulation, epithelial-mesenchymal transition (EMT) and the underlying molecular mechanisms in transforming growth factor-β (TGF-β)-stimulated TCMK-1 cells by quantitative real-time polymerase chain reaction (qPCR), Western blot analysis and immunofluorescence in vitro, and further explored the role of Tisp40 on renal fibrosis induced by ischemia-reperfusion (I/R) by qPCR, Western blot analysis, hydroxyproline analysis, Masson trichrome staining and immunohistochemistry staining in vivo., Results: The data showed that Tisp40 was upregulated in a model of renal fibrosis induced by I/R injury (IRI). Upon IRI, Tisp40-deficient mice showed attenuated renal fibrosis compared with wild-type mice. Furthermore, the expression of α-smooth muscle actin, E-cadherin, fibronectin, and collagen I was suppressed. Tisp40 overexpression aggravated ECM accumulation and EMT in the TGF-β-stimulated TCMK-1 cell line, whereas the opposite occurred in cells treated with small interfering RNA (siRNA) targeting Tisp40. Importantly, it is changes in the Smad pathway that attenuate renal fibrosis., Conclusion: These findings suggest that Tisp40 plays a critical role in the TGF-β/ Smads pathway involved in this process. Hence, Tisp40 could be a useful therapeutic target in the fight against renal tubulointerstitial fibrosis., (© 2017 The Author(s). Published by S. Karger AG, Basel.)

Background/aims: The local excision of early colorectal cancer is limited by the presence of lymph node metastasis (LNM). Signet-ring cell carcinomas (SRC) and mucinous adenocarcinomas (MAC) are two relatively infrequent histological subtypes. However, little is known about the predictors of LNM and prognosis to support the feasibility of local excision in early-stage SRC and MAC., Methods: The Surveillance Epidemiology and End Results Database were used to identify all patients with pT1 adenocarcinomas, including conventional adenocarcinoma (AC), MAC, and SRC. The prevalence of LNM was assessed, and the long-term survival rate in the above three types of colorectal cancer was calculated., Results: SRC accounted for 0.3% and MAC accounted for 4.4% of the entire cohort of colorectal adenocarcinomas. Compared to AC, MRC and SRC were more often located in the proximal colon, and exhibited a higher grade. The incidence of LNM in AC, MAC, and SRC was 10.6%, 17.2%, and 33.3% for colon cancers and 14.8%, 25.9%, and 46.2% for rectal cancers, respectively. In patients with lymph nodes resected no less than 12, incidence of LNM in AC, MRC, and SRC was 12%, 21%, and 44% for colon tumors and 17%, 30%, and 14% for rectal tumors, respectively. Although, colon patients MAC showed an entirely worse survival rate than AC, rectum patients MAC showed a similar prognosis to AC. We found that in patients with rectal tumors, SRC had a worse 3 and 5-year prognosis than AC. However, for colon cancers, the prognosis of SRC was similar to that of AC. Histology was not found to be an independent prognostic factor in multivariate survival analysis., Conclusions: MAC and SRC are two distinct subtypes of colorectal cancer that require special attention despite their relatively rare prevalence. pT1 patients with SRC of the rectum and patients with MAC of the colon have higher incidences of LNM, and with these adverse outcomes, local excision is not recommended. AlthoughMAC of the rectum and SRC of colon have a high rate of LNM, the prognosis of these types are similar to that of AC., (© 2017 The Author(s)Published by S. Karger AG, Basel.)

Background/aims: MicroRNAs (miRNAs, miRs) have emerged as important post-transcriptional regulators in various cancers. miR-543 has been reported to play critical roles in hepatocellular carcinoma and colorectal cancer, however, the role of miR-543 in the pathogenesis of prostate cancer has not been fully understood., Methods: Expression of miR-543 and Raf Kinase Inhibitory Protein (RKIP) in clinical prostate cancer specimens, two prostate cancer cell lines, namely LNCAP and C4-2B, were determined. The effects of miR-543 on proliferation and metastasis of tumor cells were also investigated with both in vitro and in vivo studies., Results: miR-543 was found to be negatively correlated with RKIP expression in clinical tumor samples and was significantly upregulated in metastatic prostate cancer cell line C4-2B compared with parental LNCAP cells. Further studies identified RKIP as a direct target of miR-543. Overexpression of miR-543 downregulated RKIP expression and promoted the proliferation and metastasis of cancer cells, whereas knockdown of miR-543 increased expression of RKIP and suppressed the proliferation and metastasis of cancer cells in vitro and in vivo., Conclusion: Our study demonstrates that miR-543 promotes the proliferation and metastasis of prostate cancer via targeting RKIP., (© 2017 The Author(s)Published by S. Karger AG, Basel.)

Objectives: (1) Determine the rate of postoperative complications, reoperation, readmission, and death after uvulopalatopharyngoplasty (UPPP) for sleep apnea through multi-institutional clinical data. (2) Compare outcomes of UPPP between multilevel and single-level procedures for the treatment of sleep apnea., Study Design: Retrospective database analysis., Methods: The American College of Surgeons National Surgical Quality Improvement Program-a nationally validated, prospective, multi-institutional database from 2005 to 2013-was analyzed for patients who underwent UPPP, per corresponding Current Procedural Terminology codes. Patients were categorized into 3 groups: UPPP alone, UPPP + nasal cavity (NC), and UPPP + base of tongue (BOT). Perioperative outcome measures of interest include surgical/medical complications, reoperation, readmission, and death. Comparisons were made among surgical groups through univariate cross-sectional analysis., Results: A total of 1079 patients underwent UPPP; 413 patients had UPPP + NC; and 200 patients had UPPP + BOT procedures. One death was reported for the entire cohort of patients. Among all 3 groups (UPPP, UPPP + NC, and UPPP + BOT), no differences were noted in the rates of medical complications (P = .445), surgical complications (P = .396), reoperation (P = .332), and readmission (P = .447). However, the length of hospital stay in days was greatest for the UPPP + BOT group (UPPP, 0.81 ± 0.69; UPPP + NC, 0.87 ± 0.90; UPPP + BOT, 1.50 ± 2.70; P < .001)., Conclusion: These national data demonstrate no significant increase in risk when UPPP is performed as a single- or multilevel procedure. When indicated, UPPP with multilevel procedures may be safely performed for treatment of sleep apnea. These data set a benchmark for perioperative risk in UPPP surgery and will prove useful for counseling patients., (© American Academy of Otolaryngology—Head and Neck Surgery Foundation 2016.)

Background: Transducin-Like Enhancer of Split protein 4 (TLE4) has been reported to be involved in some subsets of acute myeloid leukemia and colorectal cancer. In the present study, we aimed to explore the role of TLE4 in tumorigenesis and cancer progression in hepatocellular carcinoma (HCC)., Methods: The expression pattern of TLE4 in HCC was determined by Western-blot and qRT-PCR, gain-of-function and loss-of-function was used to explore the biological role of TLE4 in HCC cells. A xenograft model was established to confirm its effects on proliferation., Results: The protein expression levels of TLE4 were significantly down-regulated in HCC tissues compared to matched adjacent normal liver tissues. In vitro, down-regulation of TLE4 in Huh7 or SMMC-7721 promoted cell proliferation and ectopical expression of TLE4 in Hep3B or Bel-7404 suppressed cell proliferation. In addition, the cell colony formation ability was enhanced after down-regulation of TLE4 expression in Huh-7 but suppressed after over-expression in Hep3B. Furthermore, down-regulation of TLE4 increased the cell invasion ability, as well as increased the expression level of Vimentin and decreased that of E-cadherin, indicating a phenotype of epithelial-mesenchymal transition (EMT) in HCC cells. On the contrary, ectopical expression of TLE4 in HCC cells decreased the cell invasion ability and inhibited EMT. In vivo, compared to control group, xenograft tumor volumes were significantly decreased in TLE4 overexpression group., Conclusions: These results demonstrated that TLE4 might play important regulatory roles in cellular proliferation and EMT process in HCC., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: To understand the HIV infection status in middle aged and old men and the association between HIV infection and female sex workers in a city in Hubei province and provide evidence for the targeted prevention and control of HIV infection., Methods: Ten communities/villages were selected through stratified cluster sampling from the suburban and rural areas of the city. A total of 634 men aged ≥50 years were surveyed by using self-designed questionnaire in December, 2014., Results: The awareness rate of HIV/AIDS related knowledge was 13.3%(68/513). Among the men surveyed, 63.2%(371/587)thought they couldn't be infected with HIV, 9.1%(52/573)believed that extramarital sex is acceptable, and 32.4%(189/583)considered that commercial sexual behavior is just as well. Among the surveyed men reporting sexual behavior in the past 6 months, 6.6%(15/228)had sex with regular sexual partners, in which 63.6%(7/11)never used condoms, 21.8%(128/586)reported that some friends had commercial sexual behaviors. Among 601 men receiving HIV testing, 7 were HIV positive(1.2%). The HIV detection rates among the men living at 3 communities near red light district were 4.2%(5/119), 1.1%(1/95)and 0.5%(1/192)respectively; while no HIV infections were found in the men living at 2 towns far away from red light district. Seventy seven of 581 men surveyed(13.2%)reported to meet visiting female sex workers and they had higher HIV positive rate(5.2%, 4/77)than those without such experiences(0.6%, 3/504)(P=0.007)., Conclusion: The middle aged and old men in this city had low awareness of HIV/AIDs related knowledge, and high-risk sexual behaviors existed among them. HIV positive rate was relatively high in this population, and HIV infection might be associated with sex service.

Objectives: (1) Identify all cases of myoepithelial carcinoma of the major salivary glands from the National Cancer Data Base (NCDB). (2) Analyze the effect of grade, stage, and regional nodal metastasis on survival in myoepithelial carcinoma of the major salivary glands., Study Design: Retrospective review of NCDB., Setting: Multicenter data pooled from 1998 to 2012 in the NCDB., Methods: We identified all reported cases of myoepithelial carcinomas of the major salivary glands from the United States from 1998 to 2012 in the NCDB. Clinical parameters were then examined and analyzed for predictors of survival., Results: A total of 473 cases of myoepithelial carcinoma were identified. Of the reported cases, 38.1% were low grade; 26.7%, intermediate grade; and 35.2%, high grade. When presenting stage was examined, 24.4% were stage I; 30.6%, stage II; 22.5%, stage III; 12.2%, stage IVa; 3.0%, stage IVb; and 4.1%, stage IVc. At presentation, 18.7% of patients had regional nodal disease, and 4.5% had distant metastases. The 3- and 5-year survival rates were 73% and 64%, respectively. The presence of nodal disease significantly reduced mean survival time versus those without (64 vs 108 months, P < .001), as did high-grade disease compared with low grade (67 vs 114 months, P < .001) and stage III/IV compared with stage I/II disease (61 vs 118 months, P < .001)., Conclusions: The presence of regional nodal disease, high-grade disease, and advanced stage are predictors of lower survival in myoepithelial carcinoma. Further studies based on types of treatment are warranted., (© American Academy of Otolaryngology—Head and Neck Surgery Foundation 2016.)

Objective: (1) Determine if patients with anterior fossa spontaneous cerebrospinal fluid (SCSF) leaks demonstrate lateral skull base bone attenuation. (2) Examine the relation between body mass index (BMI; kg/m(2)) and skull base thickness., Study Design: Retrospective cohort study., Setting: Tertiary care hospital., Subjects and Methods: Retrospective review from 2004 to 2013 identified 96 patients with anterior cranial fossa SCSF leaks. A control group was identified from a consecutive series of clinic patients. Controls had no history of chronic sinonasal or temporal bone pathology and were divided according to BMI into nonobese (<30 kg/m(2)) and obese (≥30 kg/m(2)) groups. Composite skull base thickness was calculated for lateral and anterior subsites through predefined points according to previously published protocols., Results: Thirty-two patients were included in each group. Composite lateral skull base thickness was less in patients with SCSF leaks(0.7 ± 0.1 mm) when compared with nonobese controls (0.8 ± 0.1 mm, P = .004); no differences were apparent when SCSF leaks were compared with obese controls (0.7 ± 0.1 mm, P = .99). A direct relation was observed between anterior skull base and lateral skull base thickness (r = 0.48, P < .0001). An inverse correlation was noted between BMI and lateral skull base (r =-0.40, P < .0001)., Conclusions: Patients with anterior fossa SCSF leaks demonstrate attenuation of the lateral skull base. A significant correlation between anterior skull base thickness and lateral skull base thickness was observed. BMI was inversely related to lateral skull base thickness. Taken together, SCSF leaks are associated with obesity, which appears to be partly responsible for diffuse skull base erosion observed in patients with this condition., (© American Academy of Otolaryngology—Head and Neck Surgery Foundation 2016.)

Objectives/hypothesis: To determine the effect of surgeon experience with an upper airway stimulation (UAS) system on surgical time and complication rates., Study Design: Retrospective review., Methods: Surgical procedure times and complication rates observed in patients implanted at 22 study centers as part of a phase III, multicenter surgical trial of upper airway nerve stimulation therapy for obstructive sleep apnea were reviewed., Results: The study included 126 subjects who were predominantly male (83%), with a mean age of 54.5 years (range = 31-80 years), and the mean body mass index was 28.4 ± 2.6. There were an average of 5.7 (range = 1-22) surgical implants per site, with an average surgical time of 2.52 ± 0.98 hours (range = 1.08-6.0 hours). The surgical implant time decreased significantly with surgeon experience, from 2.98 ± 1.18 hours for a surgeon's first implant (n = 22) to 2.08 ± 0.55 hours for the fifth implant (n = 10, P = .025). Surgical time was inversely correlated with the site implant number (rho = -0.334, P < .001). Procedure-specific complications were uncommon and self-limited and did not decrease appreciably with increasing experience., Conclusions: Surgical time for implantation of the UAS system decreased significantly after the first five implants and then stabilized. The rate of surgical complications did not decrease with surgeon experience, although this may be attributable to the low overall rate of serious surgical complications and low number of implants at some centers., Level of Evidence: 4., (© 2015 The American Laryngological, Rhinological and Otological Society, Inc.)

Objective: (1) To identify predictors of nodal disease in parotid malignancies using various clinical and pathologic variables. (2) To examine the effect of nodal disease on overall survival (OS) in parotid cancers, Study Design: Retrospective database review., Setting: National Cancer Data Base (1998-2012)., Subjects and Methods: We identified all cases of primary parotid malignancies in the United States between 1998 and 2012 in the National Cancer Data Base. Eight histopathologies, constituting >80% of all cases, were examined for nodal metastasis and survival., Results: We identified 22,653 cases of primary parotid cancer. Eight major histologies were studied, with mucoepidermoid carcinoma (31%), acinic cell carcinoma (18%), adenocarcinoma (14%), and adenoid cystic carcinoma (9%) being most common. Regional nodal disease incidence was 24.4% overall and varied by histopathology. Salivary ductal carcinoma had the highest incidence of both nodal metastasis and occult lymph node metastasis. Overall, N0 patients lived significantly longer than N+ (5-year OS, 79% vs 40%; P < .001). Low-grade disease had significantly better survival than high-grade (5-year OS, 88% vs 69%; P < .001). Occult nodal disease was found in 10.2% and varied by histopathology., Conclusion: Regional lymph node metastasis significantly decreases survival in many parotid malignancies. High-grade cancers had higher incidences of regional disease than did low grade. Adenocarcinoma had the highest mortality when regional disease was present. Incidence of occult disease varied by histology, but incidence was <10% for all low-grade disease. High T stage and grade are significant independent predictors of nodal disease for most histopathologies., (© American Academy of Otolaryngology-Head and Neck Surgery Foundation 2015.)

Background: Both obesity and chronic rhinosinusitis (CRS) are characterized by inflammation. Furthermore, both disease processes are independently associated with decreases in quality-of-life (QOL). We sought to investigate the role of comorbid obesity in QOL outcomes in CRS patients undergoing endoscopic sinus surgery (ESS)., Methods: Adult patients with medically refractory CRS (n = 241) were prospectively enrolled into a multi-institutional treatment outcomes investigation. Body mass index (BMI) calculations were used to differentiate patient weight groups (normal weight: 18.5 to 24.9, overweight: 25.0 to 29.9; and obese: ≥30.0). Preoperative and postoperative QOL (Rhinosinusitis Disability Index [RSDI] and the 22-item Sino-Nasal Outcome Test [SNOT-22]) were evaluated compared across BMI groups and obesity subclasses., Results: The prevalence of comorbid obesity was 41% (n = 99). Higher prevalence of comorbid disease was found across increasing BMI groups including diabetes mellitus, asthma, and depression. No significant differences were found in mean preoperative QOL measures between any BMI groups. Significant improvement between preoperative and postoperative QOL mean scores (p ≤ 0.050) was found for all BMI groups. Despite no significant difference in mean QOL improvement between BMI groups (p ≥ 0.142), overweight and obese patients reported reduced relative mean percentage (%) improvement compared to normal weight participants on the RSDI total score (33% and 37% vs 55%, respectively) and SNOT-22 total score (29% and 40% vs 48%, respectively)., Conclusion: Patients with comorbid obesity experience significant improvement in average QOL gains following ESS though the percentage of relative improvement in QOL may be decreased in patients with comorbid obesity and CRS as compared to those without., (© 2015 ARS-AAOA, LLC.)

The face of head and neck cancer has changed dramatically over the past 30 years. There has been a steady decline in the number of tobacco and alcohol related squamous cell carcinomas over the past 30 years, but and increasing incidence of human papillomavirus (HPV) related cancers. Some estimates suggest that 70-90% of new oropharyngeal cancers have evidence of HPV. These patients have different demographic patterns, in that they are more likely to be younger, white adults in their 40s and 50s who are never smokers or have reduced tobacco exposure. Studies have shown that a higher number of lifetime oral sex partners (>5) and a higher number of lifetime vaginal sex partners (>25) have been associated with increased risk of HPV positive head and neck cancer. People can also reduce their risk of HPV linked head and neck cancer by receiving the HPV vaccine series prior to becoming sexually active. Recent evidence suggests HPV related head and neck cancers present with different symptoms than those caused by tobacco. The most popular test for HPV status is the p16 immunohistochemical stain because it is cheap, simple, and studies have shown it to have comparable sensitivity and specificity to the previous standards. It is widely recommended that all cancers of the oropharynx be tested for the presence of HPV, and some recommend it for all head and neck cancers. Overall 2-year and 5-year survival for HPV positive head and neck cancer is significantly greater than for HPV negative cancers, likely due to HPV positive cancers being more responsive to treatment., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

The aim of the current study was to investigate the effects and mechanism of metformin in oxidative stress and p38 mitogen-activated protein kinase (p38MAPK) expression in rat glomerular mesangial cells (MCs) cultured in a high glucose medium. Rat glomerular MCs (HBZY-1) were cultured in complete medium and divided into the following five groups: Normal control (NC), high glucose (HG), metformin-treated, SB203580-treated (SB) and N-acetylcysteine-treated (NAC). The production of intracellular reactive oxygen species (ROS) in rat glomerular MCs was measured using flow cytometry. Superoxide dismutase (SOD) activity and malondialdehyde (MDA) content in the supernatant was detected using colorimetric analysis and an ELISA, respectively. p22phox mRNA levels in rat glomerular MCs were determined using reverse transcription-quantitative polymerase chain reaction. The levels of p22phox protein and phosphorylated p38 mitogen-activated protein kinase (p-p38MAPK) protein in rat glomerular MCs were determined by western blot analysis. Compared with the NC group, the activity of SOD in the supernatant was significantly reduced, whereas the levels of MDA in the supernatant, intracellular p22phox mRNA and protein, p-p38MAPK protein in addition to ROS production in rat glomerular MCs were significantly increased in the HG group (P<0.05). When metformin was added to the high glucose medium, the activity of SOD in supernatant fluid was increased significantly, whereas a significant reduction (P<0.05) was observed in the levels of MDA in the supernatant, intracellular p22phox mRNA and protein, p-p38MAPK protein in addition to ROS production in rat glomerular MCs. These results were similar to those obtained when SB203580 or N-acetylcysteine was added to the high glucose medium (P<0.05). In conclusion, metformin was suggested to alleviate high glucose-induced oxidative stress and p-p38MAPK protein expression in rat glomerular MCs, which may contribute to its reno‑protective abilities in diabetes.

Objective: Platelet hyper-reactivity is one of the most important causes of accelerated atherosclerosis and increased risk of thrombotic vascular events associated with type 2 diabetes mellitus (T2DM). This study aimed to investigate the effects of different add-on anti-diabetic therapies on platelet function in T2DM patients., Patients and Methods: A three-group parallel study was conducted in 120 patients with T2DM (HbA1c > 7%) undergoing treatment with metformin. Patients were randomly assigned to receive add-on therapy with glipizide or pioglitazone. Markers of PF (platelet PAC-1 binding, p-selectin expression and adenosine diphosphate-induced platelet aggregation) were measured at weeks 0, 4 and 24. Primary outcome was effects of pioglitazone and glipizide on platelet aggregation. Secondary outcome was the related influencing factors of platelet aggregation., Results: There were no significant differences in baseline characteristics between glipizide and pioglitazone groups. After 24 weeks, fasting blood glucose (p < 0.01) and HbA1c (p < 0.01) were higher in pioglitazone group than those in glipizide group. Fasting insulin (p < 0.01) and HOMA-IR (p < 0.01) were lower in pioglitazone group than that in glipizide group. Markers of platelet function were significantly decreased in both groups at 24 weeks (PAC-1: pioglitazone: -63.3%; glipizide: -45.9%; p-selectin: pioglitazone: -73.9%; glipizide: -54.9%; platelet aggregation: pioglitazone: -24.1%; glipizide: -13.4%; all p < 0.01 vs. baseline), but the decrease in platelet function was more significant in pioglitazone group (p < 0.05). Multiple linear regression analyses showed that platelet aggregation was independently associated with treatment groups (p < 0.001), Triglyceride (p = 0.009) and HDL-C (p = 0.015)., Conclusions: Add-on therapy with pioglitazone may be more effective than glipizide for inhibiting platelet activation in T2DM.

Over the past years, several evidences have supported an important role of specific micronutrients, including vitamin A, vitamin D and vitamin E in immune dysfunction, vascular involvement and fibrotic changes involved in systemic sclerosis (SSc) development. In PubMed, eight clinical trials about the therapy of micronutrients on SSc patients were searched out using medical subject headings terms (SSc: "scleroderma, localized", "scleroderma, systemic", "scleroderma, diffuse" and "scleroderma, limited"; vitamins "vitamin A", "thiamin", "riboflavin", "niacin", "pantothenic acid", "vitamin B 6", "biotin", "folic acid", "vitamin B 12", "inositol", "choline", "ascorbic acid", "vitamin D", "vitamin E", "tocopherols", "vitamin K" and "vitamin P"; and minerals: "calcium", "magnesium", "potassium", "sodium", "phosphorus", "sulfur", "chlorine", "iron", "copper", "iodine", "zinc", "selenium", "manganese", "molybdenum", "cobalt", "chromium", "tin", "vanadium", "silicon", "nickel" and "fluorine"). This brief review will summarize current understanding on that for the further prospect of future studies. Though the clinical trials for the treatment of SSc with micronutrients are still in their infancy, more researches are needed to substantiate the current results and accelerate the knowledge in this field.

In order to explore the intrinsic relationship of mineral spectral characteristics and its composition, and provide the basis for the detection of mineral micro information by using hyperspectral technology, based on the thinsection analysis, the authors identified the minerals characteristics and mineral assemblages in rock samples, delineated typical chlorite minerals and divided the occurrence characteristics of chlorite. The authors measured chemical composition of 146 typical chlorite mineral particles by using electron probe micro analysis technology, and calculated the relevant chemical parameters of n(Al(IV)), n(Al(VI)), n(Fe), n(Mg), and n(Fe)/n(Fe + Mg) ratio. In addition we analysed the rock and mineral spectra, and extracted chlorite characteristic spectral parameters. The relationship between the spectra feature parameters and the main crystal chemical parameters in chlorite was analyzed. The study indicated that the diagnostic spectral wavelength of chlorites moved to long wavelength. The results have important guiding significance for identifying the alteration and rock forming mineral species, composition and structure characteristics by usinghyperspectral remote sensing technology.

The present study was conducted to reveal the effect of bags with different colors on the fruit coloration of 'Yunhongli No. 2'. The differences in fruit skin color, chlorophyll, flavonoids, total phenol, anthocyanin contents and the activities of related enzymes involved in anthocyanin synthesis among different bagging treatments were evaluated. The results showed that dark treatment at the fruit development stage was beneficial to skin coloration after bag removing. After removing bags, the anthocyanin content in the treatment of natural light was highest and the red coloration of the fruit skin were best, followed by the treatment of white bags. The different bagging treatments significantly affected the contents of chlorophyll, flavonoids, total phenol, anthocyanin in the fruit skin, thereby affected the skin coloration. The activities of related enzymes for anthocyanin synthesis showed significant differences among the different bagging treatments. The correlation analysis suggested that the anthocyanin content was significantly positively related with the activities of dihydroflavonol 4-reductase (DFR) and UDP-glucose flavonoid-3-O-glucosyltransf-erase (UFGT), however, it had no significant correlation with the activity of phenylalanin ammo-nialyase (PAL).