Extracellular vesicles derived from paclitaxel-sensitive nasopharyngeal carcinoma cells deliver miR-183-5p and impart paclitaxel sensitivity through a mechanism involving P-gp.

Paclitaxel treatment has been applied for late-stage nasopharyngeal carcinoma (NPC), but therapy failure usually occurs due to paclitaxel resistance. Besides, microRNAs (miRs) delivered by extracellular vesicles (EVs) have been demonstrated as promising biomarkers affecting cancer development. Our work clarified the role of bioinformatically predicted miR-183-5p, which could be delivered by EVs, in the paclitaxel resistance of NPC. Downstream targets of miR-183-5p were predicted in publicly available databases, followed by GO enrichment analysis. A confirmatory dual-luciferase reporter assay determined the targeting relationship between miR-183-5p and P-glycoprotein (P-gp). The shuttling of extracellular miR-183-5p was identified by immunofluorescence. EVs transferred miR-183-5p from paclitaxel-sensitive NPC cells to paclitaxel-resistant NPC cells. Furthermore, overexpression of miR-183-5p and under-expression of P-gp occurred in clinical samples and cells of NPC. High expression of miR-183-5p corresponded to better survival of paclitaxel-treated patients. The effects of manipulated expression of miR-183-5p on NPC cell activities, tumor growth, and paclitaxel resistance were investigated in vitro and in vivo. Its effect was achieved through negatively regulating drug transporters P-gp. Ectopically expressed miR-183-5p enhanced the cancer-suppressive effects of paclitaxel by targeting P-gp, corresponding to diminished cell viability and tumor growth. Taken together, this work goes to elucidate the mechanical actions of miR-183-5p delivered by EVs and its significant contribution towards paclitaxel sensitivity to NPC. 1. This study provides mechanistic insight into the role of miR-183-5p-containing EVs in NPC. 2. The intercellular transportation of miR-183-5p is mediated by EVs in NPC. 3. Overexpressing miR-183-5p facilitates the anti-tumor effects of paclitaxel in NPC. 4. miR-183-5p suppresses paclitaxel resistance of NPC cells by inhibiting P-gp.

Efficacy of Levosimendan in the Treatment of Patients With Severe Septic Cardiomyopathy.

OBJECTIVE: This study was designed to compare the effects of levosimendan and dobutamine on hemodynamics and clinical efficacy in patients with severe septic cardiomyopathy (left ventricular ejection fraction [LVEF] ≤35%). DESIGN: A prospective, single-blind, randomized controlled study. SETTING: In Baoding, China. PARTICIPANTS: Thirty patients with severe septic cardiomyopathy treated in the authors' hospital's Department of Critical Medicine from September 2018 to September 2021 were enrolled in this study. INTERVENTIONS: These patients were divided randomly into the levosimendan group and dobutamine group. The LVEF, cardiac index (CI), stroke volume index (SVI), systemic vascular resistance index, heart rate, norepinephrine dose, and lactate at the time of enrollment and the 24th hour were compared, along with myocardial injury markers on the third day, C-reactive protein, mechanical ventilation time, length of intensive care unit (ICU) stay, cost, and 28-day mortality. The primary outcome was 28-day mortality. MEASUREMENTS AND MAIN RESULTS: At the 24th hour after treatment, CI, LVEF, SVI, and fluid volume were found to be higher in the levosimendan group than in the dobutamine group, whereas the dose of norepinephrine was lower in the former rather than the latter group. On the third day of treatment, cardiac troponin I in the levosimendan group was lower than that in the dobutamine group. Although the differences in 28-day mortality, ICU stay, and ICU treatment cost between the groups were not statistically significant, the ventilator application time of the levosimendan group was significantly shorter than that of the dobutamine group. CONCLUSIONS: Compared with dobutamine, levosimendan was more effective at improving cardiac function, reducing myocardial injury, and reducing mechanical ventilation time in patients with severe septic cardiomyopathy.

Construction of High Drug Loading and Enzymatic Degradable Multilayer Films for Self-Defense Drug Release and Long-Term Biofilm Inhibition.

Bacterial infections and biofilm formation on the surface of implants are important issues that greatly affect biomedical applications and even cause device failure. Construction of high drug loading systems on the surface and control of drug release on-demand is an efficient way to lower the development of resistant bacteria and biofilm formation. In the present study, (montmorillonite/hyaluronic acid-gentamicin)10 ((MMT/HA-GS)10) organic/inorganic hybrid multilayer films were alternately self-assembled on substrates. The loading dosage of GS was as high as 0.85 mg/cm2, which could be due the high specific surface area of MMT. The obtained multilayer film with high roughness gradually degraded in hyaluronidase (HAS) solutions or a bacterial infection microenvironment, which caused the responsive release of GS. The release of GS showed dual enzyme and bacterial infection responsiveness, which also indicated good drug retention and on-demand self-defense release properties of the multilayer films. Moreover, the GS release responsiveness to E. coli showed higher sensitivity than that to S. aureus. There was only ∼5 wt % GS release from the film in PBS after 48 h of immersion, and the amount quickly increased to 30 wt % in 105 CFU/mL of E. coli. Importantly, the high drug dosage, smart drug release, and film peeling from the surface contributed to the efficient antibacterial properties and long-term biofilm inhibition functions. Both in vitro and in vivo antibacterial tests indicated efficient sterilization function and good mammalian cell and tissue compatibility.

Functional evaluation of a CAD/CAM prosthesis for immediate defect repair after total maxillectomy: a case series of 18 patients with maxillary sinus cancer.

OBJECTIVE: To evaluate the facial profiles and functional recovery of 18 patients treated by a computer-aided designed/manufactured hollow obturator prosthesis (CAD/CAM prosthesis) after total maxillectomy for malignant maxillary sinus tumor. MATERIALS AND METHODS: A retrospective observational study was performed to evaluate the facial profiles and functional recovery of 18 patients with T3-4a N0 M0 maxillary sinus cancer, who were treated by total maxillectomy and simultaneous implantation of a computer-aided designed/manufactured hollow obturator prosthesis (CAD/CAM prosthesis). Follow-ups were performed 1, 3, 6, and 12 months after surgery. Facial measurements, speech intelligibility, and chewing and swallowing functions were examined. Thirteen patients converted to a permanent prosthesis 6 months after surgery. Comparisons were made between patients with and without the CAD/CAM or permanent prosthesis at various times using SPSS13.0 statistical software (SPSS Inc., Chicago, IL, USA). RESULTS: Speech intelligibility, facial depression, and eyeball prolapse results showed improvements with prosthesis use at 1, 3, and 6 months after surgery (p < 0.05). Swallowing function improved from level V to level II-IV with prosthesis use at 1, 3, and 6 months, and reached level I or II with permanent prosthesis use at 12 months after surgery. CONCLUSIONS: Simultaneous CAD/CAM prosthesis implantation recovered the facial profile, enhanced the speaking, swallowing, and chewing functions, and improved the quality of life of patients. Tumor recurrence can be detected by direct observation of the postoperative maxillary cavity. Therefore, this operation is recommended for simultaneous excision repair and functional reconstruction after total maxillectomy. CLINICAL SIGNIFICANCE: This surgical treatment of maxillary sinus cancer is applied rarely in China, but it has a good effect based on our observation. Simultaneous CAD/CAM prosthesis implantation after total maxillectomy can recover the facial profile, enhance the speaking, swallowing, and chewing functions, and improve the quality of life of patients. Tumor recurrence can be detected by direct observation of the postoperative maxillary cavity. This technique avoids the need for dental implants because the bottom part of the prosthesis contains a palatal plate with dentures.

EP300 restores the glycolytic activity and anti-tumor function of CD8+ cytotoxic T cells in nasopharyngeal carcinoma.

Competition for glucose may metabolically limit T cells during cancer progression. This study shows that culturing in the condition medium (CM) of NPC c6661 cells restricted glycolytic and immune activities of CD8+ T cells. These cells also exhibited limited tumor-eliminating effects in mouse xenograft tumor models. Glucose supplementation restored glycolysis and immune activity of CD8+ T cells in vitro and in vivo by rescuing the expression of E1A binding protein p300 (EP300). EP300 upregulated bromodomain PHD finger transcription factor (BPTF) expression by catalyzing H3K27ac modification, and BPTF further activated AT-rich interaction domain 1A (ARID1A) transcription. Either BPTF or ARID1A knockdown in CD8+ T cells reduced their glycolytic activity, decreased the secretion of cytotoxic molecules, and blocked the tumor-killing function in mice. Overall, this study demonstrates that EP300 restores the glycolytic and anti-tumor activities of CD8+ T cells in the glucose restriction condition in NPC through the BPTF/ARID1A axis.

EFFECTS OF LEVOSIMENDAN ON DIAPHRAGMATIC DYSFUNCTION IN PATIENTS WITH SEPSIS.

ABSTRACT: Objective: In this study, our aim was to examine the effects of levosimendan on diaphragmatic dysfunction in patients with sepsis, as well as assess its impact on respiratory muscle contractility and the outcome of weaning. Methods: This was a single-blind, randomized, controlled trial. Patients with diaphragmatic dysfunction and failure of spontaneous breathing trials (SBTs) were randomly and equally assigned to the experimental and control groups. The experimental group received levosimendan at a loading dose of 6 µg/kg for 10 min, followed by a continuous infusion at 0.2 µg/kg/min. The control group received an equivalent dose of a placebo. The preadministration and postadministration respiratory mechanics parameters of the patients were recorded. Evaluation of the effect of levosimendan on patients with sepsis-induced diaphragm dysfunction comprised arterial blood gas analysis as well as ultrasound measurements of diaphragm excursion (DE), diaphragm thickness (DT), diaphragm thickening fraction (TFdi), and diaphragm-rapid shallow breathing index (D-RSBI). Results: Forty-four patients were enrolled in the study. We found that postadministration of levosimendan, the patients' tidal volume (GCSMV) increased, whereas the D-RSBI decreased, and the partial pressure of carbon dioxide (PACO 2 ) decreased when compared to the preadministration levels. Additionally, following levosimendan administration, patients showed increased DE and pressure support (PS) when compared to before administration (1.14 ± 0.177 vs. 1.22 ± 0.170 cm and 0.248 ± 0.03 vs. 0.284 ± 0.06, respectively) and decreased D-RSBI (22.76 ± 6.14 vs. 20.06 ± 6.04, respectively), all of which were statistically significant ( P < 0.05). In contrast, in the control group of patients, there were no statistically significant differences in the postadministration levels of DE, TFdi, and D-RSBI as compared to the preadministration period ( P > 0.05). Furthermore, in terms of weaning outcomes, we did not find any statistically significant difference in the number of patients in the two groups who eventually underwent weaning ( P = 0.545). Conclusion: In this study, we found that levosimendan enhanced diaphragm contractile function. However, further investigations are required to explore its effect on weaning outcomes in patients undergoing mechanical ventilation.

Implementing Foundry: A cohort study describing the regional and virtual expansion of a youth integrated service in British Columbia, Canada.

AIM: Integrated youth services (IYS) have been identified as a national priority in response to the youth mental health and substance use (MHSU) crisis in Canada. In British Columbia (BC), an IYS initiative called Foundry expanded to 11 physical centres and launched a virtual service. The aim of the study was to describe the demographics of Foundry clients and patterns of service utilization during this expansion, along with the impact of the COVID-19 pandemic. METHODS: Data were analysed for all youth (ages 12-24) accessing both in-person (April 27th, 2018-March 31st, 2021) and virtual (May 1st, 2020-March 31st, 2021) services. Cohorts containing all clients from before (April 27th, 2018-March 16th, 2020) and during (March 17th, 2020-March 31st, 2021) the COVID-19 pandemic were also examined. RESULTS: A total of 23 749 unique youth accessed Foundry during the study period, with 110 145 services provided. Mean client age was 19.54 years (SD = 3.45) and 62% identified as female. Over 60% of youth scored 'high' or 'very high' for distress and 29% had a self-rated mental health of 'poor', with similar percentages seen for all services and virtual services. These ratings stayed consistent before and during the COVID-19 pandemic. CONCLUSIONS: Foundry has continued to reach the target age group, with a 65% increase in number of clients during the study period compared with the pilot stage. This study highlights lessons learned and next steps to promote youth-centred data capture practices over time within an integrated youth services context.

Endoscopic endonasal trans-sphenoidal approach for pituitary adenomas: is one nostril enough?

BACKGROUND: Over the past decade, the endoscopic endonasal trans-sphenoidal approach has been used to resect pituitary adenomas. However, in the use of this procedure, some research teams prefer a two-nostril method, whereas other groups are in favor of the one-nostril method. Here, we present a series of pituitary adenomas and try to confirm whether or not one nostril is enough for endoscopic resection of most pituitary adenomas. METHODS: A total of 250 consecutive patients who underwent an endoscopic endonasal trans-sphenoidal approach were reviewed retrospectively, of which 200 were via the unilateral nostril (group 1) and 50 were via bilateral nostrils (group 2). Surgical and clinical outcomes were analyzed. RESULTS: For microadenomas, intrasellar macroadenomas and macroadenomas with moderate extrasellar extension, the prevalence of gross total resection (GTR), hormonal outcome and visual improvement were similar between the two groups. The one-nostril group had better results for duration of surgery and blood loss, with fewer rhinological complications. However, for macroadenomas with extensive extrasellar invasion, GTR was obtained in two of seven patients in group 2 but none in group 1. CONCLUSION: The one-nostril method, which is relatively fast and minimally invasive, is adequate for endoscopic resection of most pituitary adenomas with moderate extension.

Efficacy and toxicities of elective upper-neck irradiation versus whole-neck irradiation of the uninvolved neck in patients with nasopharyngeal carcinoma: A meta-analysis.

BACKGROUND: This meta-analysis aimed to investigate the efficacy and radiation-related toxicities of upper-neck irradiation (UNI) over whole-neck irradiation (WNI) in patients with unilateral or bilateral node-negative nasopharyngeal carcinoma. METHODS: We conducted a systematic review to identify studies comparing survival and toxicities between UNI and WNI by searching key databases up to Aug 2022. Hazard ratios (HRs) with 95% confidence intervals (CIs) for regional recurrence-free survival (RRFS), local recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), progression-free survival (PFS), and overall survival (OS) were pooled using R 4.0.5. Risk ratios (RRs) for acute and late radiation-related toxicities were also pooled. Subgroup analyses according to nodal status, radiotherapy techniques, and study type were conducted. RESULTS: Eight studies enrolling 2568 patients were included. Patients who received UNI showed similar RRFS (HR 0.99, 95% CI 0.57-1.74, P = 0.975), LRFS (HR 0.86, 95% CI 0.53-1.41, P = 0.559), DMFS (HR 0.90, 95% CI 0.63-1.29, P = 0.581), PFS (1.10, 95% CI 0.73-1.67, P = 0.642), and OS (1.03, 95% CI 0.77-1.37, P = 0.866) compared with WNI. When stratified by nodal status, the pooled HRs for RRFS in patient subgroups with stage N0 disease, stage N1 with only retropharyngeal lymph nodes metastasis, and unilateral cervical lymph node metastasis were 0.46 (95% CI 0.04-5.16, P = 0.529), 1.12 (95% CI 0.29-4.38, P = 0.872), and 1.02 (95% CI 0.48-2.16, P = 0.968) respectively, none of which reached statistical significance. UNI was associated with lower incidences of grade 1-2 hypothyroidism (RR 0.75, 95% CI 0.57-0.97, P = 0.031) and grade 1-2 dysphagia (RR 0.58, 95% CI 0.42-0.80, P < 0.001) compared with WNI. CONCLUSION: UNI had similar efficacy and fewer toxicities compared with WNI for patients with unilateral or bilateral node-negative nasopharyngeal carcinoma. The lower-neck sparing of the uninvolved neck is a valid option for N0, N1, and even unilateral N3 diseases in nasopharyngeal carcinoma.

Mendelian randomization reveals no associations of genetically-predicted obstructive sleep apnea with the risk of type 2 diabetes, nonalcoholic fatty liver disease, and coronary heart disease.

Background: Obstructive sleep apnea (OSA) has been reported to affect cardiometabolic diseases. However, whether such association is causal is still unknown. Here, we attempt to explore the effect of OSA on type 2 diabetes (T2D), nonalcoholic fatty liver disease (NAFLD) and coronary heart disease (CHD). Methods: Genetic variants associated with OSA were requested from a published genome-wide association study (GWAS) and those qualified ones were selected as instrumental variables (IV). Then, the IV-outcome associations were acquired from T2D, NAFLD and CHD GWAS consortia separately. The Mendelian randomization (MR) was designed to estimate the associations of genetically-predicted OSA on T2D, NAFLD and CHD respectively, using the inverse-variance weighted (IVW) method. We applied the Bonferroni method to adjust the p-value. Besides, MR-Egger regression and weighted median methods were adopted as a supplement to IVW. The Cochran's Q value was used to evaluate heterogeneity and the MR-Egger intercept was utilized to assess horizontal pleiotropy, together with MR-PRESSO. The leave-one-out sensitivity analysis was carried out as well. Results: No MR estimate reached the Bonferroni threshold (p < 0.017). Although the odds ratio of T2D was 3.58 (95% confidence interval (CI) [1.06, 12.11], IVW-p-value = 0.040) using 4 SNPs, such causal association turned insignificant after the removal of SNP rs9937053 located in FTO [OR = 1.30 [0.68, 2.50], IVW p = 0.432]. Besides, we did not find that the predisposition to OSA was associated with CHD [OR = 1.16 [0.70, 1.91], IVW p = 0.560] using 4 SNPs. Conclusion: This MR study reveals that genetic liability to OSA might not be associated with the risk of T2D after the removal of obesity-related instruments. Besides, no causal association was observed between NAFLD and CHD. Further studies should be carried out to verify our findings.

Mendelian randomization eradicates the causal relationship between educational attainment, household income, and oropharyngeal cancer.

Background: It was reported that educational attainment and household income are associated with oropharyngeal cancer. However, whether such an association is causal is still unknown. Methods: The Mendelian randomization (MR) design was performed to disentangle their causal relationship. Initially, genetic variants proxied for educational attainment and household income were extracted from the largest genome-wide association studies (GWAS), and two oropharyngeal GWAS datasets were used in the discovery and validation stages separately. A reverse MR analysis was carried out to judge whether oropharyngeal cancer affects educational attainment and household income. The results from the two stages were combined using meta-analysis. The heterogeneity and horizontal pleiotropy were appraised using several methods. Results: All selected genetic variants were valid. In the discovery stage, genetically elevated years of education might decrease the risk of oropharyngeal cancer (IVW OR = 0.148 [0.025, 0.872], p-value = 0.035), while such a result became insignificant in the validation stage (IVW p-value >0.05). Household income cannot change the risk of oropharyngeal cancer at both stages. The reverse MR suggested that oropharyngeal cancer should slightly alter household income (IVW OR = 1.001 [1.000, 1.003], p-value = 0.036) in the discovery set, but the result cannot be replicated in the validation stage. The meta-analysis did not find any significant results either. The results were also assessed by sensitivity analyses, and there was no heterogeneity or horizontal pleiotropy in the analyses. The statistical powers were all above 80% at the discovery stage. Conclusions: There should be no causal association between educational attainment, household income, and oropharyngeal cancer.

Understanding Mobile Health and Youth Mental Health: Scoping Review.

BACKGROUND: A total of 75% of people with mental health disorders have an onset of illness between the ages of 12 and 24 years. Many in this age group report substantial obstacles to receiving quality youth-centered mental health care services. With the rapid development of technology and the recent COVID-19 pandemic, mobile health (mHealth) has presented new opportunities for youth mental health research, practice, and policy. OBJECTIVE: The research objectives were to (1) synthesize the current evidence supporting mHealth interventions for youths who experience mental health challenges and (2) identify current gaps in the mHealth field related to youth's access to mental health services and health outcomes. METHODS: Guided by the methods of Arksey and O'Malley, we conducted a scoping review of peer-reviewed studies that used mHealth tools to improve youth mental health (January 2016-February 2022). We searched MEDLINE, PubMed, PsycINFO, and Embase databases using the following key terms: (1) mHealth; (2) youth and young adults; and (3) mental health. The current gaps were analyzed using content analysis. RESULTS: The search produced 4270 records, of which 151 met inclusion criteria. Included articles highlight the comprehensive aspects of youth mHealth intervention resource allocation for targeted conditions, mHealth delivery methods, measurement tools, evaluation of mHealth intervention, and youth engagement. The median age for participants in all studies is 17 (IQR 14-21) years. Only 3 (2%) studies involved participants who reported their sex or gender outside of the binary option. Many studies (68/151, 45%) were published after the onset of the COVID-19 outbreak. Study types and designs varied, with 60 (40%) identified as randomized controlled trials. Notably, 143 out of 151 (95%) studies came from developed countries, suggesting an evidence shortfall on the feasibility of implementing mHealth services in lower-resourced settings. Additionally, the results highlight concerns related to inadequate resources devoted to self-harm and substance uses, weak study design, expert engagement, and the variety of outcome measures selected to capture impact or changes over time. There is also a lack of standardized regulations and guidelines for researching mHealth technologies for youths and the use of non-youth-centered approaches to implementing results. CONCLUSIONS: This study may be used to inform future work as well as the development of youth-centered mHealth tools that can be implemented and sustained over time for diverse types of youths. Implementation science research that prioritizes youths' engagement is needed to advance the current understanding of mHealth implementation. Moreover, core outcome sets may support a youth-centered measurement strategy to capture outcomes in a systematic way that prioritizes equity, diversity, inclusion, and robust measurement science. Finally, this study suggests that future practice and policy research are needed to ensure the risk of mHealth is minimized and that this innovative health care service is meeting the emerging needs of youths over time.

Expression of concern: Bacterial self-defense antibiotics release from organic-inorganic hybrid multilayer films for long-term anti-adhesion and biofilm inhibition properties.

Expression of concern for 'Bacterial self-defense antibiotics release from organic-inorganic hybrid multilayer films for long-term anti-adhesion and biofilm inhibition properties' by Qingwen Xu, Nanoscale, 2017, 9, 19245-19254, https://doi.org/10.1039/C7NR07106J.

Development and validation of a nomogram to estimate future risk of type 2 diabetes mellitus in adults with metabolic syndrome: prospective cohort study.

OBJECTIVES: To develop and validate the 4-year risk of type 2 diabetes mellitus among adults with metabolic syndrome. DESIGN: Retrospective cohort study of a large multicenter cohort with broad validation. SETTINGS: The derivation cohort was from 32 sites in China and the geographic validation cohort was from Henan population-based cohort study. RESULTS: 568 (17.63) and 53 (18.67%) participants diagnosed diabetes during 4-year follow-up in the developing and validation cohort, separately. Age, gender, body mass index, diastolic blood pressure, fasting plasma glucose and alanine aminotransferase were included in the final model. The area under curve for the training and external validation cohort was 0.824 (95% CI, 0.759-0.889) and 0.732 (95% CI, 0.594-0.871), respectively. Both the internal and external validation have good calibration plot. A nomogram was constructed to predict the probability of diabetes during 4-year follow-up, and on online calculator is also available for a more convenient usage ( https://lucky0708.shinyapps.io/dynnomapp/ ). CONCLUSION: We developed a simple diagnostic model to predict 4-year risk of type 2 diabetes mellitus among adults with metabolic syndrome, which is also available as web-based tools ( https://lucky0708.shinyapps.io/dynnomapp/ ).

Obstructive sleep apnea and the risk of Alzheimer's disease and Parkinson disease: A Mendelian randomization study OSA, Alzheimer's disease and Parkinson disease.

BACKGROUND: Previous studies reported that obstructive sleep apnea (OSA) was associated with neurodegenerative diseases. However, whether these associations are causal are still unsettled. In our study, we investigated the causal effects of genetically-predicted OSA on Alzheimer's disease (AD) and Parkinson disease (PD). METHODS: We implemented two-sample Mendelian randomization to judge causation using summary statistics from three independent and large genome-wide association studies on OSA (cases n = 16,761, controls n = 201,194), AD (cases n = 71,880, controls n = 383,378) and PD (cases n = 33,774, controls n = 449,056). Four single nucleotide polymorphisms (SNPs) with genome-wide significance associated with OSA served as instrumental variables. We prioritized the inverse variance weighted method when generating unconfounded estimates. Besides, MR-Egger regression, weighted mode, and weighted median methods were adopted as a supplement to the inverse variance weighted method. RESULTS: We found no evidence supporting significant causal relationships between OSA and AD or PD among European population. The risk ratio of AD was 0.99 (95% confidence interval (CI) [0.92,1.08]) and that of PD was 0.82 (95%CI [0.47, 1.40]). Results from alternative approaches were generally consistent with that of the inverse variance weighted method. CONCLUSION: The present study found no evidence for causal associations between OSA and the risk of AD or PD in individuals of European ancestry.

IL-17 signaling pathway plays a key role in laryngeal squamous cell carcinoma with ethnic specificity.

Laryngeal squamous cell carcinoma (LSCC) is a common aggressive head and neck squamous cell carcinoma (HNSCC) and racial disparities have been reported to exist in it. However, its molecular mechanism and associated ethnic specificity are still unclear. Here, we leveraged mRNA expression data from 2 gene expression omnibus datasets (GSE142083 & GSE117005) of Chinese samples and the cancer genome atlas (TCGA) datasets of Caucasian samples to demonstrate the expression signature of LSCC. The GSE142083 dataset was used as the discovery set since it had 53 pairs of LSCC tissues and matched adjacent normal tissues, and the GSE117005 dataset was treated as the validation set with 5 pairs of tissues. Differential gene expression analysis and enrichment pathway analysis were performed. Besides, we employed weighted gene co-expression network analysis to identify hub genes in validated pathways. The TCGA datasets were used to evaluate ethnic specificity. Immunohistochemistry (IHC) was employed to further validate the hub gene. Overall, the IL-17 signaling pathway was significantly enriched for upregulated genes in two Chinese datasets while not in TCGA datasets; and IL17RC, MAPK3, S100A8, MMP3, CXCL8, and TNFA1P3 were hub genes regulating such pathway. Therein, IL17RC might be the most important one and the IHC results displayed that the IL17RC gene upregulated in the LSCC tissue. IL-17 signaling pathway has an ethnicity-specific effect in LSCC where it is upregulated in the Chinese while not in the Caucasians and IL17RC might play a key role. Targeting genes located in the IL-17 signaling pathway may be beneficial for Chinese LSCC patients.

Renal outcomes and prognostic factors in patients with type-2 diabetes and chronic kidney disease confirmed by renal biopsy.

AIM: To evaluate the renal outcomes and prognostic factors among patients with type-2 diabetes (T2D) and biopsy-confirmed diabetic nephropathy (DN), non-diabetic renal disease (NDRD) and DN mixed with NDRD (MIX). DESIGN AND METHODS: Patients with both T2D and chronic kidney disease (CKD) who underwent renal biopsy between January 2014 and December 2016 were recruited in this prospective observational study. Participants were divided into DN group, NDRD group, or MIX group according to the baseline pathological diagnosis. The primary endpoint was a composite renal event of end-stage renal disease (ESRD) or ⩾ 40% reduction in estimated glomerular filtration rate (eGFR). RESULTS: Among the 292 participants included, 153 (52.4%) belonged to the DN group, 30 (10.3%) belonged to the NDRD group, and 109 (37.3%) belonged to the MIX group. During the median follow-up of 27 months, the adverse renal events occurred in 132 (44.2%) patients. Compared with NDRD group, the multiple adjusted hazard ratios (HRs) for renal events in patients with DN and MIX groups were 3.900 (95% confidence interval [CI]: 1.103-13.788) and 2.691 (95% CI: 0.662-10.936), respectively. Baseline lower eGFR (HR: 1.159, 95% CI: 1.060-1.266), severe proteinuria (HR: 2.047, 95% CI: 1.227-3.416), lower hemoglobin (HR: 1.170, 95% CI: 1.008-1.267), and a family history of diabetes (HR: 1.138, 95% CI: 1.008-2.285) were independent predictors for adverse renal outcomes in patients with DN. CONCLUSION: In patients with T2D and CKD, pure DN and MIX group displayed a worse renal prognosis than NDRD group. Worse renal function, severe proteinuria, lower hemoglobin, and a family history of diabetes may be associated with adverse renal outcomes in patients with DN.

Clinical observation of soft palate-pharyngoplasty in the treatment of obstructive sleep apnea hypopnea syndrome in children.

BACKGROUND: Childhood obstructive sleep apnea hypopnea syndrome (OSAHS) is a common clinical disease that can cause serious complications if not treated in time. The preferred treatment for OSAHS in children is surgery. AIM: To observe the effects of soft palate-pharyngoplasty on postoperative outcome, pharyngeal formation, and possible complications. METHODS: A total of 150 children with snoring, hernia, and mouth breathing were selected. A polysomnography test was performed to confirm the diagnosis of OSAHS. The children were randomly divided into experimental and control groups. The experimental group underwent adenoidectomy, tonsillectomy, and soft palate-pharyngoplasty. The control group underwent adenoidectomy and tonsillectomy. The t-test and chi-square test were used to compare conditions such as postoperative fever, postoperative hemorrhage, and pharyngeal reflux. Postoperative efficacy and complications were interrogated and observed in the form of outpatient follow-up and telephone follow-up at 6 mo and 1 year after surgery. The curative effects were divided into two groups: Cure (snoring, snoring symptoms disappeared) and non-cure. RESULTS: The effective rate of the experimental group was significantly higher than that of the control group, but the difference was not statistically significant (P > 0.05). The incidence of postoperative bleeding was lower in the experimental group. There was no postoperative pharyngeal reflux in either group. In the experimental group, the incidence of hyperthermia (body temperature exceeded 38.5 °C) was lower than that in the control group. The difference in postoperative swallowing pain scores between the experimental and control groups was significant. CONCLUSION: Soft palate-pharyngoplasty can more effectively enlarge the anteroposterior diameter and transverse diameter of the isthmus faucium. Compared with surgery alone, it can better treat OSAHS in children, improve the curative effect, reduce the risk of perioperative bleeding, close the surgical cavity, reduce the risk of postoperative infection, reduce the proportion of postoperative fever, and accelerate healing. Although this process takes more time, it is simple, safe, and effective.

Dual drug delivery from hydrophobic and hydrophilic intraocular lenses: in-vitro and in-vivo studies.

Posterior capsule opacification (PCO) still remains the most frequent long term complication after cataract surgery, while endophthalmitis is rare but severe and should be prevented at all cost. Intraocular lenses (IOLs) with different designs (eg. edge and body-haptics angle) and materials (acrylic hydrophobic and acrylic hydrophilic surfaces) have been studied to reduce PCO. For the prevention of endophthalmitis, intracameral injection followed or not by topical treatment with antibiotics and anti-inflammatories are usually prescribed. The objective of this work was to investigate the use of IOLs as controlled release platforms of two drugs, the antibiotic moxifloxacin (MXF) and the anti-inflammatory ketorolac (KTL) that could advantageously substitute the usual treatment. Two types of IOLs were chosen, hydrophobic and hydrophilic. Hydrophobic IOLs have shown better results in the prevention of PCO because they adhere better to the posterior capsular bag, while hydrophilic IOLs are advised in the case of patients with uveitis, glaucoma or diabetes. The IOLs were loaded with MXF + KTL and sterilized by high hydrostatic pressure. Both IOLs reduced the tendency for adhesion of LECs. In vivo tests were done to compare the concentration of the drugs in the aqueous humor obtained after eye drops administration and drug-loaded IOLs implantation. The developed IOLs were able to release MXF and KTL at therapeutic levels, in a sustained way, which contrasts with the eye drops prophylaxis. No PCO signs were detected and histological analyses demonstrated biocompatibility of these devices.