Identifying the pathophysiological traits of obstructive sleep apnea during dexmedetomidine sedation.

Dexmedetomidine (DEX) has been described as a safe sedative in clinical practice, but its effects on the pathophysiological traits of obstructive sleep apnea (OSA) are unclear. We estimated the effects of DEX sedation on the four key pathophysiological traits of OSA (pharyngeal collapsibility, dilator muscle function, arousal threshold, and loop gain) in adult patients with OSA by conducting a secondary analysis of a prospective diagnostic trial. Pathophysiological traits estimated from polysomnography and the respiratory parameters under natural sleep and DEX-induced sleep were compared. Bivariate and multivariate linear regression analyses were used to estimate the relationship between pathophysiological traits and OSA severity for both sleep states. Adult patients with OSA had a significantly higher pharyngeal collapsibility (Vpassive : 44.9 [15.7 to 53.8] vs. 53.3 [34.2 to 66.3] %eupnea , p < 0.001), arousal threshold (178.5 [132.5 to 234.6] vs. 140.5 [123.2 to 192.3] %eupnea , p < 0.001), and loop gain (LG1: 0.74 ± 0.25 vs. 0.60 ± 0.17, p < 0.001; LGn: 0.52 ± 0.12 vs. 0.44 ± 0.08, p < 0.001) during DEX-induced sleep compared with natural sleep. There was no significant difference in dilator muscle function or PSG respiratory parameters between natural versus DEX-induced sleep states. Bivariate regression analysis showed varying degrees of correlation between OSA traits and severity. Multiple regression analysis indicated that collapsibility was the strongest predictor of the apnea-hypopnea index for both sleep states. Dexmedetomidine sedation in patients with OSA increased the pharyngeal collapsibility without impairing dilator muscle function, while elevating arousal threshold and increasing loop gain.

Exposure-Response Analysis and Mechanism of Ginkgolide B's Neuroprotective Effect in Acute Cerebral Ischemia/Reperfusion Stage in Rat.

Ginkgolide B (GKB) is a well-established neuroprotectant for acute ischemia stroke. However, its cerebral exposure and real-time response remain elusive in acute ischemia/reperfusion stage, and it hinders its usage in therapeutic window of ischemia stroke. Therefore, we investigate the exposure-response relationship of GKB (10 mg/kg, intravenously (i.v.)) as well as its neuroprotective mechanism in acute ischemia/reperfusion rats. Cerebral and plasma exposure of GKB is comparatively explored in both of normal rats and acute ischemia/reperfusion rats. Correspondingly, neurological function and brain jury indexes were assessed at each time point, and superoxide dismutase (SOD), malondialdehyde (MDA), platelet activator factor (PAF) and thromboxane A2 (TXA2) are indexed as pharmacological response to GKB. Exposure-response relationships are analyzed by using linear regression. Additionally, cerebral expressions of proteins in PAF-regulated pathways are tested at each time point. Results show cerebral and plasma concentrations of GKB are much higher in acute ischemia/reperfusion rats than those in normal rats. Cerebral infarction, neurological function (NF) score, abnormal PAF and excessive MDA are significantly alleviated in 24 h after GKB injection, and PAF is reduced in exposure-response manner with significant concentration-response relationship (R2 = 0.9123). Regarding downstream proteins in intracellular PAF-regulated pathway, GKB progressively inhibits Bax, Caspase-3, p-p65 and p-IKK, while gradually restoring LC3B, p62 and p-mammalian target of rapamycin (mTOR) to the basic level within 24 h. Conclusively, GKB exhibits greater cerebral exposure in acute ischemia/reperfusion rats and neuroprotective effect through reducing PAF in exposure-response manner and mediating PAF-regulated intracellular signaling pathways. Our finding highlights clinical implications of GKB in therapeutic time window of ischemic stroke.

Acute and subacute inhalation toxicity assessment of WS-23 in Sprague-Dawley rats.

2-isopropyl-N,2,3-trimethylbutyramide (WS-23) is a well-known artificial synthesis cooling agent widely used in foods, medicines, and tobaccos. As a commonly cooling agent in e-cigarette liquids, WS-23 has led to concerns about the inhalation toxicity with the prosperous of e-cigarettes in recent years. Thus, the aim of this study is to assess the acute and subacute inhalation toxicity of WS-23 in Sprague-Dawley (SD) rats according to the Organization for Economic Cooperation and Development (OECD) guidelines. In the acute toxicity study, there was no mortality and behavioral signs of toxicity at the limit test dose level (340.0 mg/m3 ) in the exposure period and the following 14-day observation period. In the subacute inhalation toxicity study, there was no significant difference observed in the body weights, feed consumption, and relative organ weights. Haematological, serum biochemical, urine, and bronchoalveolar lavage fluid (BALF) analysis revealed the non-adverse effects after 28-day repeated WS-23 inhalation (342.85 mg/m3 ), accompanied by slight changes in few parameters which returned to normal during the 28-day recovery period. The histopathologic examination also did not show any differences in vital organs. In conclusion, the maximum tolerated dose for WS-23 acute inhalation is not less than 340.0 mg/m3 , and the No Observed Adverse Effect Level (NOAEL) of WS-23 subacute inhalation was determined to be over 342.85 mg/m3 .

The cost-effectiveness analysis of drug therapy versus surgery for symptomatic adenoid hypertrophy by a Markov model.

PURPOSE: Adenoid hypertrophy (AH) is common among young children. Adenoid-based surgery and drug therapy could be applied for symptomatic AH patients, yet the treatment decision is difficult to make due to the diverse cost and efficacy between these two treatments. METHODS: A Markov simulation model was designed to estimate the cost-effectiveness (CE) of the adenoid-based surgery and the drug therapy for symptomatic AH patients. Transition probabilities, costs and utilities were extracted from early researches and expert opinions. Simulations using two set of parameter inputs for China and the USA were performed. Primary outcome was cost per QALY gained over a 6-year period. Deterministic and probabilistic sensitivity analyses were also conducted. RESULTS: The utility for the surgery group and the drug group were 4.10 quality-adjusted life years (QALYs) and 3.58 QALYs, respectively. The cost of the surgery group was more than that of the drug group using model parameters specific to China ($1069.0 vs. $753.7) but was less for the USA ($1994.4 vs. $3977.7). Surgery was dominant over drug therapy when US specific parameters were used. Surgery group had an ICER of $604.0 per QALY when parameters specific to China was used. CONCLUSION: Surgery is cost-effective in the simulations for both China and the USA at WTP thresholds of $9633.1 and $62,517.5, respectively.

Leptin Promoted IL-17 Production from ILC2s in Allergic Rhinitis.

BACKGROUND: Interleukin-17 plays important roles in allergic diseases. Several studies proved that leptin promoted Th17 immune responses by inducing RORγt transcription. ILC2 is an important member of the early stage of immune response. Therefore, we aimed to explore the effect of leptin on the IL-17 production by ILC2 in AR in this study. METHODS: Fifteen AR patients and fifteen healthy controls were enrolled. Serum leptin levels were measured, and their correlation with the frequency of IL-17+ ILC2 cells was analyzed using enzyme-linked immunosorbent assay (ELISA) and flow cytometry. ILC2 was stimulated by leptin, and the expression of IL-17, IL-5, and IL-13 was detected by ELISA. The correlated pathways were confirmed by real-time PCR. RESULTS: We found that serum leptin and the frequency of IL-17-producing ILC2s in AR were significantly higher compared with those in controls. After being incubated with leptin, the frequency of IL-17+ ILC2 cells and IL-17 production from ILC2 was upregulated compared with that in controls. We also found that leptin induced RORγt and Ahr expression by ILC2. Moreover, leptin-induced IL-17-producing ILC2 concomitantly expressed IL-5 and IL-13. CONCLUSIONS: Our data provide preliminary evidence that leptin-induced IL-17 production from ILC2 cells is dependent on RORγt and Ahr expression and the blockade of leptin may be a promising target for the treatment of AR.

[Analysis on new research and development ideas and technical points of traditional Chinese medicine for prevention and treatment of chronic heart failure].

Chronic heart failure(CHF), a serious and end stage of various heart diseases, is a common chronic cardiovascular disease in the 21 st century. Literature data show that the 5-year mortality rate of hospitalized patients with heart failure is as high as 50%. Nowadays, the development of drugs treating heart failure has become a hot spot, meanwhile, traditional Chinese medicine(TCM) has shown the advantages in the treatment of chronic heart failure. In this article, four stages to develop traditional Chinese medicine for chronic heart failure were proposed. Firstly, discuss and screen ideas and methods with regard to the development of TCM and its prescriptions based on clinical needs. Secondly, study the preparation process and quality control method by referring to the existing clinical background of TCM prescriptions and analyzing the chemical compositions and pharmacological action characteristics of each herb in the prescription. Then, design non-clinical evaluation programs and carry out researches on pharmacodynamics and toxicology by combining the experience of clinical use of TCM prescriptions and future clinical positioning, and gradually adjust and improve the programs during implementation. Finally, conduct clinical trial application(IND) by submitting registration application data which are base on the clinical drug experience, preclinical research pharmacy, main pharmacodynamics, safety test results of the prescription, clinical positioning, and reasonable clinical trial plan designed by the theory of TCM. After passing the IND technical review, the clinical trial study shall be officially launched to achieve the desired results and obtain effective Chinese patent medicines for heart failure treatment.

Epigenetic Modification of Enhancer of Zeste Homolog 2 Modulates the Activation of Dendritic Cells in Allergen Immunotherapy.

BACKGROUND: Allergen immunotherapy (AIT) is the only etiological and potentially curative therapy for allergic rhinitis (AR). OBJECTIVES: We sought to investigate the role of epigenetic regulator enhancer of zeste homolog 2 (EZH2) in the activation of dendritic cells (DCs) in AIT. METHOD: In this study, EZH2 expression in circulating myeloid DCs (mDCs) and plasmacytoid DCs (pDCs) were evaluated using flow cytometry. Clinical information from 56 AR patients receiving AIT was collected, including 30 subjects with subcutaneous immunotherapy (SCIT) and 26 subjects with sublingual immunotherapy (SLIT). In vitro, the effect of EZH2 inhibitor, 3 Deazaneplanocin A (DZNep), on the phenotypic and functional activation of monocyte-derived DCs (moDCs) was evaluated. RESULTS: EZH2 expression in circulating mDCs and pDCs were both negatively correlated to treatment time of AIT (r = -0.39, p = 0.003 and r = -0.47, p = 0.0002, respectively). Furthermore, there was a higher correlation between EZH2 expression and AIT treatment time in the SCIT group compared to that of the SLIT group in mDCs (r = -0.42, p = 0.02 vs. r = -0.23, p = 0.26)and pDCs (r = -0.52, p = 0.003 vs. r = -0.33, p = 0.10). In vitro, the co-stimulatory molecules on moDCs, such as CD80, CD86, and CD83, were significantly inhibited by DZNep in a dose-dependent manner. The -DC-driven T-cell proliferation was suppressed by DZNep (MD = 22.88, 95% CI 7.809-37.96, p < 0.05). CONCLUSIONS: Our study shows that EZH2, which is required in the activation of DCs, mediates the epigenetic modification in AIT and stresses the importance of patient adherence during AIT.

Concomitant corticosteroid nasal spray plus antihistamine (oral or local spray) for the symptomatic management of allergic rhinitis.

The purpose of this study was to perform a systematic review and meta-analysis of randomized controlled trials (RCTs) to compare the symptomatic management of corticosteroid nasal spray plus antihistamine (oral or local spray) with that of either therapy given alone, or placebo in patients with allergic rhinitis (AR). The PRISMA guidelines for meta-analysis reporting were followed. Total nasal symptom scores and individual nasal symptom scores were pooled after assessing heterogeneity among studies. The pooled estimates were expressed as weighted mean differences (WMD) between treatments. A total of ten studies fulfilled eligibility. Three trials studied the combination therapy of corticosteroid nasal spray and oral antihistamine. Pooled results of two trials failed to show significant difference on total nasal symptoms between combination therapy and intranasal corticosteroid alone (WMD = -0.20, 95 % CI -0.38 to -0.01, P = 0.04). The qualitative analysis showed that combination therapy has greater efficacy than oral antihistamines alone or placebo in improving symptoms. Seven trials investigated corticosteroid nasal spray plus antihistamine nasal spray. The cumulative meta-analysis of six RCTs revealed that combination therapy was superior to solo intranasal corticosteroid (WMD = -1.16, 95 % CI -1.49 to -0.83, P < 0.00001), solo intranasal antihistamine (WMD = -1.73, 95 % CI -2.08 to -1.38, P < 0.00001), and placebo (WMD = -2.81, 95 % CI -3.16 to -2.47, P < 0.00001) in improving total nasal symptom scores. Intranasal corticosteroid plus oral antihistamine have similar efficacy to intranasal corticosteroid alone, greater efficacy than oral antihistamines alone or placebo in reducing nasal symptoms for AR patients. Intranasal corticosteroid plus intranasal antihistamine are significantly superior to either therapy given alone, or placebo.

Azelastine enhances the clinical efficacy of glucocorticoid by modulating MKP-1 expression in allergic rhinitis.

Azelastine was suggested as a supplementary choice of glucocorticoid for the control of moderate to severe allergic rhinitis (AR). However, the underlying mechanism has not been completely understood. In this study, primary cultured nasal epithelial cells and bronchial epithelial cells were stimulated with proinflammatory cytokines (IL-1ß and IL-17A) and anti-inflammatory agents (azelastine and budesonide) in vitro. The expression of intercellular adhesion molecule 1 (ICAM-1) and mitogen-activated protein kinase phosphatase-1 (MKP-1) was examined using qPCR and ELISA, respectively. Moreover, the additive effects of azelastine and budesonide nasal spray on nasal ICAM-1 level and total nasal symptom scores were evaluated in six uncontrolled severe AR patients by budesonide nasal spray alone. We found azelastine significantly inhibited cytokine-induced ICAM-1 upregulation, which is reversed by MKP-1 silencing. Azelastine and budesonide additively increased MKP-1 expression and inhibited ICAM-1 expression in vitro. After treatment for two consecutive weeks, combined azelastine and budesonide nasal spray significantly decreased nasal ICAM-1 level and TNSS in six uncontrolled AR patients. Our findings suggested that azelastine is able to additively enhance the anti-inflammatory effect of budesonide by modulating MKP-1 expression, which may implicate in the treatment of uncontrolled severe AR.

Increased expression of aldehyde dehydrogenase 1 A1 in nasopharyngeal carcinoma is associated with enhanced invasiveness.

Increased expression of aldehyde dehydrogenase 1 (ALDH1) has recently been reported in several cancers. However, whether member A1 of aldehyde dehydrogenase 1 (ALDH1A1) is involved in the formation of nasopharyngeal carcinoma (NPC) remains unknown. To investigate the expression of ALDH1A1 in NPC and its association with the tumorigenesis of NPC, we examined the expression of ALDH1A1 in NPC specimens using immunohistochemistry (IHC), quantitative RT-PCR (qRT-PCR) and Western blot. Moreover, we sorted ALDH1A1(high) cells from NPC cell line CNE-2 by flow cytometry and examined the expression of primitive embryonic stem cell markers OCT4, SOX2 and Nanog. Finally, we investigated the capacities of growth, proliferation, colony- formation and tumorigenesis of ALDH1A1(high) cells in vitro and in vivo. We found ALDH1A1 was significantly increased in human NPC samples via IHC, qRT-PCR and Western blot (p < 0.05). ALDH1A1(high) cells sorted from NPC cell line CNE-2 by flow cytometry had higher expression of primitive embryonic stem cell markers OCT4, SOX2 and Nanog, and showed enhanced capacities of growth, proliferation, colony formation and tumorigenesis in vitro and in vivo when compared with ALDH1A1(low) cells (p < 0.05). Our findings indicated that increased expression of ALDH1A1 in NPC was associated with enhanced invasiveness.

Osteopontin promotes EZH2 expression and tumor progression in nasopharyngeal carcinoma.

OBJECTIVE: To evaluate the possible mechanism of osteopontin (OPN) in the tumor progression of nasopharyngeal carcinoma (NPC). METHODS: Twenty NPC specimens and 10 normal biopsy specimens were analyzed, and the expression of OPN and enhancer of zeste homolog 2 (EZH2) was examined by immunohistochemical staining. Moreover, the expression of EZH2 in NPC cell lines was examined using quantitative reverse transcription polymerase chain reaction and Western blot analysis in the presence of recombinant human (rh) OPN and specific inhibitors. NPC cell migration and invasion were evaluated using a transwell chamber in the presence of rhOPN and/or EZH2 siRNA. RESULTS: The immunoreactivity of OPN and EZH2 was significantly enhanced in NPC specimens compared with the normal controls (p < 0.05). EZH2 expression in NPC specimens was significantly associated with OPN expression and tumor stage (p < 0.05). Moreover, rhOPN significantly stimulated EZH2 expression in the NPC cell line through a MAPK-mediated pathway and significantly stimulated migration and invasion of the NPC cell line (p < 0.05), which was notably inhibited by EZH2 siRNA transfection (p < 0.05). CONCLUSION: Our findings suggest that OPN may promote tumor progression of NPC through an EZH2-dependent pathway.

[Study on prevention effect of huoluotongnao tablet on stroke (II)].

OBJECTIVE: To study the prevention effect of Huoluotongnao tablet on stroke. METHODS: Bilateral common carotid artery ligation and reperfusion injury model and reperfusion injury in focal cerebral ischemia-induced thrombosis line method rat model were used. RESULTS: Huoluotongnao tablet could significantly reduce the pathological injury of rat brain tissue changes of these two models, and increase the activity of SOD and decrease the content of MDA in the brain tissue and plasma of rats. The brain water content of treatment groups were significantly reduced. The behavioral index and cerebral infarction range index were effectively improved in the middle cerebral artery occlusion reperfusion model rats. CONCLUSION: Huoluotongnao tablet has certain prevention effect on stroke.

tsRNA modifications: An emerging layer of biological regulation in disease.

BACKGROUND: Transfer RNA (tRNA)-derived small RNA (tsRNA) represents an important and increasingly valued type of small non-coding RNA (sncRNA). The investigation of tRNA and tsRNA modification crosswalks has not only provided novel insights into the information and functions of tsRNA, but has also expanded the diversity and complexity of the tsRNA biological regulation network. AIM OF REVIEW: Comparing with other sncRNAs, tsRNA biogenesis show obvious correlation with RNA modifications from mature tRNA and harbor various tRNA modifications. In this review, we aim to present the current aspect of tsRNA modifications and that modified tsRNA shape different regulatory mechanisms in physiological and pathological processes. KEY SCIENTIFIC CONCEPTS OF REVIEW: Strategies for studying tsRNA mechanisms include its specific generation and functional effects induced by sequence/RNA modification/secondary structure. tsRNAs could harbor more than one tRNA modifications such as 5-methylcytosine (m5C), N1-methyladenosine (m1A), pseudouridine (Ψ) and N7-methylguanosine (m7G). This review consolidates the current knowledge of tRNA modification regulating tsRNA biogenesis, outlines the functional roles of various modified tsRNA and highlights their specific contributions in various disease pathogenesis. Therefore, the improvement of tsRNA modification detection technology and the introduction of experimental methods of tsRNA modification are conducive to further broadening the understanding of tsRNA function at the level of RNA modification.

Preventive and Therapeutic Effects of Crocetin in Rats with Heart Failure.

Gardenia is both a food and medicine plant. It is widely used for cardiovascular protection, and its main bioactive ingredient is crocetin. This study aims to observe the therapeutic effects of crocetin on chronic heart failure in rats induced by various etiologies. It further compares the efficacy differences between preventative and treatment administration, varying dosages, and treatment durations, to provide improved guidance for medication in heart failure rats and determine which categories of chronic heart failure rats might benefit most from crocetin. Chronic heart failure models induced by abdominal aorta constriction, renal hypertension, and coronary artery ligation were constructed. By examining cardiac function, blood biochemistry, and histopathology, the study assessed the preventive and therapeutic effects of crocetin on load-induced and myocardial ischemia-induced heart failure. The results showed that in all three models, both treatment and preventative administration of crocetin significantly improved chronic heart failure in rats, especially in preventative administration. The results indicate crocetin may be beneficial for improving symptoms and functional capacity in rats with heart failure. Furthermore, long-term administration was more effective than short-term administration across all three rat models, with therapeutic onset observed over 6 weeks.

[Chinese medicine formula 1 regulating immunity and anti-oxidation experiments in mice].

OBJECTIVE: To observe the effect of immunoregulation and anti-oxidation of Zhongyaofangji NO1 (ZYFJ). METHODS: 1. SPF BALB/C mice were randomly divided into control group (distilled water), positive control group (Broken Spore), ZYFJ low dose group (0.35 g/kg), middle dose group (0.70 g/kg) and high dose group (1.40 g/kg), with intragastric administration 1 time/d for 30d; The spleen and thymus index, ability of spleen lymphocyte proliferation, phagocytosing chicken red blood cell (CRBC) of abdominal macrophage cell, carbon clearance were investigated. 2. SPF BALB/C mice were divided into normal control group, model control group (D-galactose induced peroxidation damage), model plus ZYFJ low dose, middle dose and high dose group, model plus positive control group (Broken Spore), with drug administration 1 time/d for 30 d. SOD activity, MDA and LPO content in brain tissue were tested while Nrf2 [Nuclear factor (erythroi D-derived 2)-like 2] protein expression in brain tissue nucleus was tested by western blotting. RESULTS: The thymus index and spleen index in groups of ZYFJ high dose and positive control were higher than those in control group, the ability of lymphocyte proliferation and phagocytosis of macrophages were increased in all the other groups significantly compared with control group; The activity of SOD and Nrf2 protein expression level in brain tissue of model mice was increased, MDA and LPO contents were reduced in ZYFJ middle and high dose as well as positive control significantly, while the MDA content was reduced and Nrf2 protein was increased in low dose group. CONCLUSION: Appropriate dose of ZYFJ1 has good effect of immunoregulation, and plays a role of anti-oxidation probably by regulating Nrf2 protein expression in brain tissue and related signaling pathway.

[Study on prevention effect of huoluotongnao tablet on stroke (I)].

OBJECTIVE: To study the prevention effect of Huoluotongnao tablet on stroke. METHODS: Thrombosis on arteriovenous shunt rats model, platelet aggregation and hypertension combined high cholesterol rats model were used. RESULTS: Huoluotongnao tablet high and low dosage could inhibit the formation of arteriovenous thrombosis and platelet aggregation significantly ,the inhibition rate was 17.71%, 22.69%, 20.34% and 24.43%, respectively. Pretreatment of Huoluotongnao tablet could inhibit the formation of arteriovenous thrombosis significantly; The levels of CHOz in all treatment groups of hypertension combined high cholesterol rats model were decreased significantly,the levels of TGz and LDL-C were decreased in the high dosage group,the blood pressure was decreased in the middle dosage group. eta bL, eta P and eta r (B/P) were decreased in the middle and high dosage groups. eta bM, AI and CY were decreased in the middle and high dosage groups. Huoluotongnao tablet had effect on blood lipid,blood pressure and hemorheology and in a dose-dependence manner. Its minimal effecting dose was the middle dose. g/kg (crude drug) and has certain prevention effect on stroke. CONCLUSION: Huoluotongnao tablet's minimal effecting dose is 1.28

Upfront Surgery Versus Definitive Radiotherapy: Competing Risk Analyses in Early Stage Oropharyngeal Cancer.

OBJECTIVE: To compare the survival outcomes of early-stage oropharyngeal cancer (OPC) patients treated with upfront surgery versus definitive radiotherapy (RT). STUDY DESIGN: Retrospective observational study. SETTING: Publicly available database. METHODS: A total of 1877 patients with T1-2N0-1M0 OPC were retrieved from the Surveillance, Epidemiology, and End Results database. Primary endpoints were cancer-specific and noncancer mortalities, which were estimated using cumulative incidence function and compared by Gray's test. Univariate and multivariate Fine-Gray subdistribution hazard models were used to estimate the effects of treatment modality on mortality. Subgroup analyses were performed in propensity-score-matched cohorts. All the analyses were conducted separately in human papillomavirus (HPV)-negative and HPV-positive cohorts. RESULTS: In the HPV-negative cohort, definitive RT was independently associated with increased risk of cancer-specific mortality (adjusted subdistribution hazard ratio [SHR], 2.29; 95% confidence interval [CI], 1.42-3.68; p = .001) and noncancer mortality (adjusted SHR, 2.74; 95% CI, 1.50-5.02; p = .001). In the HPV-positive cohort, definitive RT and upfront surgery could achieve similar cancer-specific and noncancer survival outcomes. CONCLUSION: Upfront surgery is associated with lower cancer-specific and noncancer mortality in HPV-negative early-stage OPC patients. However, in the setting of HPV-positive early-stage OPC with better prognosis, the 2 treatment modalities have similar efficacy in terms of cancer-specific and noncancer survival outcomes. In the future, carefully designed prospective clinical trials are needed to confirm our findings.

Effect of Bilateral Vocal Fold Microsuturing on Voice Quality Improvement in Patients With Anterior Glottic Webs: A Retrospective Observational Study.

PURPOSE: This study was performed to introduce a modified procedure involving a combination of bilateral vocal fold mucosal flaps and microsurgical sutures for the management of anterior glottic webs and to study its efficacy in decreasing the recurrence rate and improving voice quality. METHODS: We retrospectively reviewed 102 patients with anterior glottic webs who underwent surgical treatment by a carbon dioxide laser incision with or without microsurgical suturing in our hospital from May 2014 to April 2021. We focused on the reoperation rate and the voice outcomes based on the 30-item Voice Handicap Index. RESULTS: This study included 102 patients with anterior glottic webs, which were caused by papilloma excision and endoscopic laryngocarcinoma resection in 97 (95.1%) of the 102 patients; less common causes were infection and traumatic injury. All incisions were performed along the midline with a carbon dioxide laser under microscopy and a self-retaining laryngoscope; 37 (36.3%) patients underwent microsurgical suturing and 65 (63.7%) patients did not. The microsuture group had a lower reoperation rate (χ2= 7.069, P = 0.0078) and higher voice quality (t = 2.054, P = 0.0462) than the non-microsuture group. CONCLUSIONS: We introduced a modified procedure that can both decrease the recurrence rate and improve the voice quality in patients with anterior glottic webs. Hence, this combination therapy involving bilateral vocal fold mucosal flaps and microsurgical sutures is worthy of clinical application and promotion.

CD69 and SBK1 as potential predictors of responses to PD-1/PD-L1 blockade cancer immunotherapy in lung cancer and melanoma.

Background: PD-1/PD-L1 blockade is a promising immunotherapeutic strategy with the potential to improve the outcomes of various cancers. However, there is a critically unmet need for effective biomarkers of response to PD-1/PD-L1 blockade. Materials and methods: Potential biomarkers of response to PD-1/PD-L1 blockade were obtained from the Cancer Treatment Response gene signature Database (CTR-DB). A comprehensive pan-cancer analysis was done on The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) datasets. Correlations between gene expression and infiltration by immune cells were assessed using TIMER, EPIC, MCPcounter, xCell, CIBERSORT, and quanTIseq. Immunophenoscore (IPS) was used to assess the potential application of the biomarkers to all TCGA tumors. Results: Analysis of CTR-DB data identified CD69 and SBK1 as potential biomarkers of response to PD-1/PD-L1 blockade. Correlation analysis revealed that in various TCGA cancer datasets, CD69 expression level correlated positively with most immune checkpoints and tumor-infiltrating immune cells, while SBK1 expression level correlated negatively with infiltrating immune cells. IPS analysis demonstrated the ability of CD69 and SBK1 to predict PD-1/PD-L1 blockade responses in various cancers. Conclusion: CD69 and SBK1 are potential predictors of response to cancer immunotherapy using PD-1/PD-L1 blockade. These biomarkers may guide treatment decisions, leading to precise treatment and minimizing the waste of medical resources.

Dexmedetomidine-induced polysomnography as a diagnostic method in obstructive sleep apnea: a reliable alternative method?

BACKGROUND: Under-diagnosis of obstructive sleep apnea (OSA) is common because of the demanding and time-consuming nature of polysomnography (PSG). Herein, we assessed the utility of a short daytime dexmedetomidine-induced PSG for diagnosis of OSA in adults. METHODS: This was a single-center, prospective, diagnostic trial. We evaluated 86 patients using a full overnight PSG and a short diurnal drug-induced PSG (DIPSG). DIPSG was induced by continuous intravenous dexmedetomidine infusion. Sedation depth was monitored and maintained using the Narcotrend index (50-70). Diagnostic performance for DIPSG with different apnea-hypopnea index (AHI) cut-off values were calculated. Bland-Altman plots used for analysis. Sleep architecture and position were compared. RESULTS: We studied 47 OSA patients and 39 healthy volunteers. Sensitivity and specificity for detection of OSA by DIPSG were 92% and 79%, respectively, for an AHI cut-off value of 5, 90% and 77%, respectively, for an AHI cut-off value of 15, and 95% and 85%, respectively, for an AHI cut-off value of 30. The DIPSG bias was -5 (-25; 15) for AHI and -3 (-13; 7) for minimal oxygen saturation. N2 sleep was increased (32.9% vs. 50.75%, respectively; p < 0.01) and REM sleep was decreased (21.35% vs. 1.24%, respectively; p < 0.01) during DIPSG. Twenty-eight (33%) participants had postural shifts during DIPSG. No significant adverse events were observed during DIPSG. CONCLUSIONS: Dexmedetomidine-induced PSG had a good sensitivity and specificity, and can be used as a screening tool for diagnosis of OSA in adults. CHINESE CLINICAL TRIAL REGISTRATION: ChiCTR1900024044.