Discovery of a New Compound, Erinacerin W, from the Mycelia of Hericium erinaceus, with Immunomodulatory and Neuroprotective Effects.

One new compound with an isoindolinone skeleton, along with erinacines A, C, and S, was isolated from the mycelia of Hericium erinaceus, an edible fungus with a long history of use in traditional Chinese medicine. Based on analysis of MS and NMR spectral data, the structure of the compound was identified as (2E,6E)-8-(2-(1-carboxy-3-methylbutyl)-4,6-dihydroxy-1-oxoisoindolin-5-yl)-2,6-dimethylocta-2,6-dienoic acid. In light of this discovery, we have given this compound the name erinacerin W. Using a co-culture in vitro LPS-activated BV2 microglia-induced SH-SY5Y neuroinflammation model, the results showed that erinacerin W demonstrated protection against the LPS-activated BV-2 cell-induced overexpression of IL-6, IL-1ß, and TNF-α on SH-SY5Y cells. This finding may provide potential therapeutic approaches for central nervous disorders.

The trade-off of post-mastectomy radiotherapy usage for the breast cancer patients aged 70 years or older: a study based on SEER database.

BACKGROUND: This study aimed to investigate the role of post-mastectomy radiotherapy (PMRT) in the female aged 70 years or older diagnosed with breast cancer, which is still controversial. METHODS: This retrospective study enrolled female breast cancer women aged 70 + years following mastectomy from the Surveillance, Epidemiology, and End Results (SEER) database. Propensity score matching (PSM) was performed to reduce covariable imbalance. A nomogram was created to predict the 1,3,5-years overall survival (OS) and divide patients into three risk groups. RESULTS: After matching, PMRT were associated with significant improvement in breast cancer-specific survival (BCSS) and OS (p < 0.001). By contrast, the BCSS and OS benefit from PMRT were not significant in patients with T1N1 tumor (BCSS: HR = 0.716, p = 0.249;OS:HR = 0.908, p = 0.572), and T2N1 tumor (BCSS:HR = 0.866, p = 0.289;OS:HR = 0.879, p = 0.166). Stratified by subtype, the HR+/HER-2- subtype and the HR-/HER-2- subtype (all p < 0.001) have a significant prolonged survival, yet not significant BCSS difference are shown in the HER-2 + tumor. In the low-risk group as determined by the nomogram, the use of PMRT did not significantly improve OS (p = 0.203). CONCLUSIONS: This study demonstrated that PMRT improves the survival of females with elderly breast cancer, while for T1-2N1 breast cancer patients, the omission of PMRT could be considered. Furthermore, the nomogram we constructed could be used as a decision tool for the omission of PMRT in low-risk elderly patients.

Prognosis and local treatment strategies of breast cancer patients with different numbers of micrometastatic lymph nodes.

BACKGROUND: Lymph node micrometastasis is an important prognostic factor in breast cancer, but patients with different numbers of involved lymph nodes are all divided into the same N1mi stage without distinction. We designed this study to compare the prognosis and local treatment recommendations of N1mi breast cancer patients with different numbers of micrometastatic lymph nodes. PATIENTS AND METHODS: A total of 27,032 breast cancer patients with T1-2N1miM0 stage from the Surveillance, Epidemiology, and End Results (SEER) database (2004-2019) who underwent breast surgery were included in this retrospective study. Patients were divided into three groups for prognosis comparison according to the number of micrometastatic lymph nodes: N1mi with 1 (Nmi = 1), 2 (Nmi = 2), or more (Nmi ≥ 3) involved lymph nodes. We explored the characteristics and survival outcomes of the population receiving different local treatments, including different axillary surgery types and whether receiving radiotherapy or not. Univariate and multivariate Cox proportional hazards regression analysis were used to compare the overall survival (OS) and breast cancer-specific survival (BCSS) in different groups. Stratified analyses and interaction analyses were also applied to explore the predictive significance of different involved lymph nodes numbers. Propensity score matching (PSM) method was utilized to balance the differences between groups. RESULTS: Univariate and multivariate Cox regression analysis indicated that nodal status was an independent prognostic factor. After adjustment for other prognostic factors, there was a significant difference in prognosis between Nmi = 1 group and Nmi = 2 group [adjusted hazard ratio (HR) 1.145, 95% confidence interval (CI): 1.047-1.251, P = 0.003], and patients with Nmi ≥ 3 group had a significantly poorer prognosis (adjusted HR 1.679, 95% CI 1.589-2.407; P < 0.001). The proportion of N1mi patients only underwent sentinel lymph nodes biopsy (SLNB) gradually increased from 2010 (Ptrend < 0.001). After adjusting for other factors, N1mi patients who underwent axillary lymph nodes dissection (ALND) was associated with significant survival benefit than SLNB (adjusted HR 0.932, 95%CI 0.874-0.994; P = 0.033), the same goes for receiving radiotherapy (adjusted HR 1.107, 95%CI 1.030-1.190; P = 0.006). Further stratified analysis showed that in the SLNB subgroup, radiotherapy was associated with a significant survival benefit (HR 1.695, 95%CI 1.534-1.874; P < 0.001), whereas in the ALND subgroup, there was no significant prognostic difference with or without radiotherapy (HR 1.029, 95%CI 0.933-1.136; P = 0.564). CONCLUSION: Our study indicates that the increasing number of lymph node micrometastases was associated a worse prognosis of N1mi breast cancer patients. In addition, ALND does provide a significant survival benefit for these patients, while the benefit from local radiotherapy may be of even greater importance.

GSN gene frameshift mutations in Alzheimer's disease.

BACKGROUND: The pathogenic missense mutations of the gelsolin (GSN) gene lead to familial amyloidosis of the Finnish type (FAF); however, our previous study identified GSN frameshift mutations existed in patients with Alzheimer's disease (AD). The GSN genotype-phenotype heterogeneity and the role of GSN frameshift mutations in patients with AD are unclear. METHOD: In total, 1192 patients with AD and 1403 controls were screened through whole genome sequencing, and 884 patients with AD were enrolled for validation. Effects of GSN mutations were evaluated in vitro. GSN, Aß42, Aß40 and Aß42/40 were detected in both plasma and cerebrospinal fluid (CSF). RESULTS: Six patients with AD with GSN P3fs and K346fs mutations (0.50%, 6/1192) were identified, who were diagnosed with AD but not FAF. In addition, 13 patients with AD with GSN frameshift mutations were found in the validation cohort (1.47%, 13/884). Further in vitro experiments showed that both K346fs and P3fs mutations led to the GSN loss of function in inhibiting Aß-induced toxicity. Moreover, a higher level of plasma (p=0.001) and CSF (p=0.005) GSN was observed in AD cases than controls, and a positive correlation was found between the CSF GSN and CSF Aß42 (r=0.289, p=0.009). Besides, the GSN level was initially increasing and then decreasing with the disease course and cognitive decline. CONCLUSIONS: GSN frameshift mutations may be associated with AD. An increase in plasma GSN is probably a compensatory reaction in AD, which is a potential biomarker for early AD.

Doubly-robust estimator of the difference in restricted mean times lost with competing risks data.

In the context of competing risks data, the subdistribution hazard ratio has limited clinical interpretability to measure treatment effects. An alternative is the difference in restricted mean times lost (RMTL), which gives the mean time lost to a specific cause of failure between treatment groups. In non-randomized studies, the average causal effect is conventionally used for decision-making about treatment and public health policies. We show how the difference in RMTL can be estimated by contrasting the integrated cumulative incidence functions from a Fine-Gray model. We also show how the difference in RMTL can be estimated by using inverse probability of treatment weighting and contrasts between weighted non-parametric estimators of the area below the cumulative incidence. We use pseudo-observation approaches to estimate both component models and we integrate them into a doubly-robust estimator. We demonstrate that this estimator is consistent when either component is correctly specified. We conduct simulation studies to assess its finite-sample performance and demonstrate its inherited consistency property from its component models. We also examine the performance of this estimator under varying degrees of covariate overlap and under a model misspecification of nonlinearity. We apply the proposed method to assess biomarker-treatment interaction in subpopulations of the POPLAR and OAK randomized controlled trials of second-line therapy for advanced non-small-cell lung cancer.

Rapid detection of viruses: Based on silver nanoparticles modified with bromine ions and acetonitrile.

Nearly 200 million people have been diagnosed with COVID-19 since the outbreak in 2019, and this disease has claimed more than 5 million lives worldwide. Currently, researchers are focusing on vaccine development and the search for an effective strategy to control the infection source. This work designed a detection platform based on Surface-Enhanced Raman Spectroscopy (SERS) by introducing acetonitrile and calcium ions into the silver nanoparticle reinforced substrate system to realize the rapid detection of novel coronavirus. Acetonitrile may amplify the calcium-induced hot spots of silver nanoparticles and significantly enhanced the stability of silver nanoparticles. It also elicited highly sensitive SERS signals of the virus. This approach allowed us to capture the characteristic SERS signals of SARS-CoV-2, Human Adenovirus 3, and H1N1 influenza virus molecules at a concentration of 100 copies/test (PFU/test) with upstanding reproduction and signal-to-noise ratio. Machine learning recognition technology was employed to qualitatively distinguish the three virus molecules with 1000 groups of spectra of each virus. Acetonitrile is a potent internal marker in regulating the signal intensity of virus molecules in saliva and serum. Thus, we used the SERS peak intensity to quantify the virus content in saliva and serum. The results demonstrated a satisfactory linear relationship between peak intensity and protein concentration. Collectively, this rapid detection method has a broad application prospect in clinical diagnosis of viruses, management of emergent viral infectious diseases, and exploration of the interaction between viruses and host cells.

Myeloid ecotropic viral integration site-1 inhibition promotes apoptosis, suppresses proliferation of acute myeloid leukemia cells, accentuates the effects of anticancer drugs.

To investigate the effects of myeloid ecotropic viral integration site-1 (MEIS1) on the proliferation and apoptosis of acute myeloid leukemia (AML) cells and the anticancer effects of the drug, we screened Kasumi-6, KG-1, and Kasumi-1 cells using quantitative reverse transcription polymerase chain reaction. Kasumi-6 and Kasumi-1 cells were subjected to human antigen R (HuR)-mediated interference (IV). Hexokinase 2 (HK2) expression and phosphorylation of protein kinase B (p-AKT) and mammalian target of rapamycin (p-mTOR) were observed with Western blotting. Cell proliferation was assessed using Cell Counting Kit-8, apoptosis was examined using Hoechst 33,258 staining, and glucose uptake was detected with a colorimetric biochemical assay kit. We found that, among the three cell lines tested, MEIS1 expression was highest in Kasumi-1 cells, which were therefore selected for subsequent experiments. Kasumi-1 cells receiving IV showed significantly decreased proliferation (p < 0.05) and increased apoptosis compared to the control group. Compared with the controls, IV significantly increased the expression of HK2, p-AKT, p-mTOR, multidrug resistance-associated protein 1 and P-glycoprotein (P < 0.05), but decreased glucose uptake. Treatment with adriamycin, daunorubicin and imatinib resulted in a progressive increase in inhibition of cell proliferation, with the IV group showing the highest inhibition rate among the three groups (P < 0.05). Thus, inhibition of MEIS1 activity promoted apoptosis, inhibited the proliferation of Kasumi-1 and Kasumi-6 cells, and increaseed the anticancer effect of the drugs, suggesting that inhibition of MEIS1 may be a potential strategy for the treatment of AML.

Effects of astaxanthin on plasma membrane function and fertility of boar sperm during cryopreservation.

Mammalian sperm is highly susceptible to reactive oxygen species (ROS) during the cryopreservation process. Astaxanthin (AST), a red pigment of the carotenoid family, is recognized as having a variety of beneficial biological activities and effects, including antioxidant, anticancer, anti-diabetic, and anti-inflammatory. The present study aimed to investigate whether the presence of AST protected boar sperm from ROS stress during cryopreservation. Boar sperm was diluted with a freezing medium supplemented with different concentrations of AST (0, 0.5, 1, 2, or 5 µM). The addition of AST, especially at a concentration of 2 µM, exerted positive effects on post-thaw sperm motility parameters. Meanwhile, sperm plasma membrane integrity and acrosome integrity of post-thaw sperm were significantly increased, while lipid peroxidation was inhibited in response to 2 µM AST treatment. Interestingly, compared to the control, supplementation with 2 µM AST increased unsaturated fatty acids (UFAs) levels and decreased saturated fatty acids (SFAs) content in post-thaw sperm, leading to a decreased ratio of SFAs/UFAs in the AST group. In conclusion, the addition of AST to freezing extenders inhibited lipid peroxidation and regulated fatty acid composition of the sperm membrane, improved post-thaw sperm quality, and had no adverse effect on boar sperm in vitro fertilization (IVF) capacity and potential for embryonic development. Our data provide a novel insight into understanding the mechanisms of AST concerning protecting boar sperm quality against ROS damage during cryopreservation.

Nutritional and 13-Week Subchronic Toxicological Evaluation of Lignosus rhinocerotis Mycelium in Sprague-Dawley Rats.

Lignosus rhinocerotis (Tiger's Milk mushroom) is a novel mushroom with sclerotium belonging to the Polyporaceae family and has been reported widely to possess anti-cancer, anti-cough, antioxidant, gastro-protective, immuno-modulating, and neurite-stimulating properties. As numerous studies have proven the tremendous medicinal values of L. rhinocerotis, it is necessary to understand its nutrition as well as its safety for the recipient. Previous research on L. rhinocerotis has mainly focused on the naturally occurring sclerotium and may have overlooked mushroom mycelia from submerged liquid fermentation, which ensures a high uniform quantitative biomass production as well as a high biological value. Hence, this is the first report on the evaluation of nutrition and 13-week repeated oral toxicity of L. rhinocerotis mycelium (LRM). The LRM powder contained 9.0 ± 4.2% moisture, 1.9 ± 1.3% ash, 1.6 ± 2.2% crude lipid, 8.4 ± 5.3% crude protein, 79.3 ± 4.6% carbohydrate, and 364 kcal/100 g energy. The total free amino acid ranged from 349 to 5636 mg/100 g and the umami index of freeze-dried LRM powder was 0.37. For safety assessment, ninety-six rats were divided into four groups, each consisting of twelve male and twelve female rats. Test articles were administered by oral gavage to rats at 850, 1700, and 3400 mg/kg body weight/day for 13 weeks and reverse osmosis water was used as the control. All animals survived to the end of the study. During the experiment period, no abnormal changes were observed in clinical signs, body weight, or ophthalmological examinations. No adverse or test article-related differences were found in urinalysis, hematology, or serum biochemistry parameters between the treatment and control groups. Necropsy and histopathological examination indicated no treatment-related changes. According to the above results, the no-observed-adverse-effect level (NOAEL) of L. rhinocerotis was identified to be greater than 3400 mg/kg body weight (BW)/day in Sprague-Dawley rats.

Detecting Lesional Granulysin Levels for Rapid Diagnosis of Cytotoxic T lymphocyte-Mediated Bullous Skin Disorders.

BACKGROUND: Bullous skin disorders are induced by different pathomechanisms and several are emergent, including Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). Rapid diagnostic methods for SJS/TEN or cytotoxic T-lymphocyte (CTL)-mediated bullous disorders are crucial for early treatment. Granulysin, primarily expressed by CTLs, is a specific cytotoxic protein responsible for SJS/TEN and similar skin reactions. OBJECTIVE: To assess granulysin levels in blister fluids to differentiate SJS/TEN and similar CTL-mediated bullous reactions from other autoimmune bullous disorders. METHODS: Using ELISA, we measured granulysin in blister fluids from patients with bullous skin disorders, including SJS/TEN, erythema multiforme major, bullous fixed-drug eruption, bullous lupus erythematosus, paraneoplastic pemphigus, pemphigus vulgaris, bullous pemphigoid, purpura fulminans-related bullae, and hand-foot syndrome/hand-foot-skin reactions. We compared serum and blister granulysin levels in patients with SJS/TEN presenting varying severity, monitoring serial granulysin levels from acute to late stages. RESULTS: Overall, 144 patients presenting with bullous skin disorders were enrolled. Blister granulysin levels (mean ± SD) in CTL-mediated disorders, including TEN (n = 28; 3938.7 ± 3475.7), SJS-TEN overlapping (n = 22; 1440.4 ± 1179.6), SJS (n = 14; 542.0 ± 503.2), erythema multiforme major (n = 7; 766.3 ± 1073.7), generalized bullous fixed-drug eruption (n = 10; 720.4 ± 858.3), and localized bullous fixed-drug eruption (n = 16; 69.0 ± 56.4), were significantly higher than in non-CTL-mediated bullous disorders (P < .0001), including bullous lupus erythematosus (n = 3; 22.7 ± 20.1), paraneoplastic pemphigus (n = 3; 20.3 ± 8.6), pemphigus vulgaris (n = 3; 4.4 ± 2.8), bullous pemphigoid (n = 18; 4.0 ± 2.7), purpura fulminans (n = 4; 5.9 ± 5.5), and hand-foot syndrome/hand-foot-skin reactions (n = 6; 4.6 ± 3.5). Blister granulysin levels correlated with clinical severity of SJS/TEN (P < .0001). CONCLUSIONS: Determination of blister granulysin levels is a noninvasive and useful tool for rapid differential diagnosis of SJS/TEN and other similar CTL-mediated bullous skin disorders for treatment selection.

Induction of G2/M Phase Arrest by Diosgenin via Activation of Chk1 Kinase and Cdc25C Regulatory Pathways to Promote Apoptosis in Human Breast Cancer Cells.

The anti-tumor activity of diosgenin, a new steroidal constituent present in fenugreek, on two human breast cancer cell lines, MCF-7 and Hs578T, was studied. Diosgenin treatment resulted in cell growth inhibition, cell cycle arrest, and apoptosis in concentration- and time-dependent manners in both cell lines. Western blot analyses of whole cell lysates for cell cycle proteins showed that diosgenin altered phosphorylated cyclin checkpoint1 (p-Chk1Ser345) and cyclin B expression, which resulted in G2/M phase blockade. Mechanistically, Cdc25C-Cdc2 signaling was involved in inactivating Chk1Ser345 by p53-dependence in MCF-7 cells and p21-dependence in Hs578T cells that are p53-deficient. Moreover, diosgenin induced a significant loss of the mitochondrial membrane potential in breast cancer cells, and prominently affected cell death through down-regulation of the anti-apoptotic protein, Bcl-2. This released cytochrome c and activated the caspase signaling cascade. Taken together, these findings reveal that the anti-proliferative activity of diosgenin involves the induction of G2/M phase arrest via modulating the Cdc25C-Cdc2-cyclin B pathway and mitochondria-mediated apoptosis in human breast cancer cell lines. This suggests the potential usefulness of diosgenin in treating breast cancer.

EV71 3C protease induces apoptosis by cleavage of hnRNP A1 to promote apaf-1 translation.

Enterovirus 71 (EV71) induces apoptosis to promote viral particle release. Earlier work showed that EV71 utilizes its 3C protease to induce apoptosis in a caspase-3-dependent pathway, though the mechanism is unknown. However, work from Vagner, Holcik and colleagues showed that host protein heterogeneous ribonucleoprotein A1 (hnRNP A1) binds the IRES of cellular apoptotic peptidase activating factor 1 (apaf-1) mRNA to repress its translation. In this work, we show that apaf-1 expression is essential for EV71-induced apoptosis. EV71 infection or ectopic expression of 3C protease cleaves hnRNP A1, which abolishes its binding to the apaf-1 IRES. This allows IRES-dependent synthesis of apaf-1, activation of caspase-3, and apoptosis. Thus, we reveal a novel mechanism that EV71 utilizes for virus release via a 3C protease-hnRNP A1-apaf-1-caspase-3-apoptosis axis.

Coupled Kinetics Model for Microbially Mediated Arsenic Reduction and Adsorption/Desorption on Iron Oxides: Role of Arsenic Desorption Induced by Microbes.

The dynamic behavior of arsenic (As) species is closely associated with iron mineral dissolution/transformation in the environment. Bacterially induced As(V) desorption from iron oxides may be another important process that facilitates As(V) release from iron oxides without significant reductive dissolution of iron oxides. Under the impact of bacterially induced desorption, As kinetic behavior is controlled by both the microbial reduction of As(V) and the As(III)&As(V) reactions on iron oxide surfaces. However, there is still a lack of quantitative understanding on the coupled kinetics of these processes in complex systems. We developed a quantitative model that integrated the time-dependent microbial reduction of As(V) with nonlinear As(III)&As(V) adsorption/desorption kinetics on iron oxides under the impact of bacterially induced As(V) desorption. We collected and modeled literature data from 11 representative studies, in which microbial reduction reactions occurred with minimal iron oxide dissolution/transformation. Our model highlighted the significance of microbially induced As(V) desorption and time-dependent changes of microbial reduction rates. The model can quantitatively assess the roles and the coupling of individual reactions in controlling the overall reaction rates. It provided a basis for developing comprehensive models for As cycling in the environment by coupling with other chemical, physical, and microbial processes.

Histone Deacetylase Inhibitor, Trichostatin A, Synergistically Enhances Paclitaxel-Induced Cytotoxicity in Urothelial Carcinoma Cells by Suppressing the ERK Pathway.

Trichostatin A (TSA), an antifungal antibiotic derived from Streptomyces, inhibits mammalian histone deacetylases, and especially, selectively inhibits class I and II histone deacetylase (HDAC) families of enzymes. TSA reportedly elicits an antiproliferative response in multifarious tumors. This study investigated the antitumor effects of TSA alone and in combination with paclitaxel when applied to two high-grade urothelial carcinoma (UC) cell lines (BFTC-905 and BFTC-909). Fluorescence-activated cell sorting, flow cytometry, and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium assay were used to assess TSA's cytotoxicity and effects on apoptosis induction. TSA induced synergistic cytotoxicity, when combined with paclitaxel (combination index < 1), resulted in concomitant suppression of paclitaxel-induced activation of phospho-extracellular signal-regulated kinase (ERK) 1/2. A xenograft nude mouse model confirmed that TSA enhances the antitumor effects of paclitaxel. These findings demonstrate that the administration of TSA in combination with paclitaxel elicits a synergistic cytotoxic response. The results of this study indicate that the chemoresistance of UC could be circumvented by combining HDAC inhibitors to target the ERK pathway.

The Medication Risk of Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis in Asians: The Major Drug Causality and Comparison With the US FDA Label.

Specific ethnic genetic backgrounds are associated with the risk of Stevens-Johnson syndrome / toxic epidermal necrolysis (SJS/TEN) especially in Asians. However, there have been no large cohort, multiple-country epidemiological studies of medication risk related to SJS/TEN in Asian populations. Thus, we analyzed the registration databases from multiple Asian countries who were treated during 1998-2017. A total 1,028 SJS/TEN cases were identified with the algorithm of drug causality for epidermal necrolysis. Furthermore, those medications labeled by the US Food and Drug Administration (FDA) as carrying a risk of SJS/TEN were also compared with the common causes of SJS/TEN in Asian countries. Oxcarbazepine, sulfasalazine, COX-II inhibitors, and strontium ranelate were identified as new potential causes. In addition to sulfa drugs and beta-lactam antibiotics, quinolones were also a common cause. Only one acetaminophen-induced SJS was identified, while several medications (e.g., oseltamivir, terbinafine, isotretinoin, and sorafenib) labeled as carrying a risk of SJS/TEN by the FDA were not found to have caused any of the cases in the Asian countries investigated in this study.

An accessory right hepatic artery derived from the superior mesenteric artery for anterior right liver lobe supply: a case report.

PURPOSE: During the last decades, it has been established that there are numerous individual anatomical variations of the arterial blood supply in human liver. In the present study, we examined the liver vascularization of an intrahepatic cholangiocarcinoma patient. METHODS: For surgical planning, an enhanced CT scan was performed and a three-dimensional model of liver vascularization constructed. RESULTS: The patient was diagnosed as a Michel's type VII hepatic artery variation. An accessory right hepatic artery arose from the superior mesenteric artery and had distributed into the right anterior liver to provide the blood supply of segments V and VIII, which was more medial than the territory of the right hepatic artery coming from the proper hepatic artery. At the same time, an accessory left hepatic artery originated from the left gastric artery. CONCLUSION: We present a case in which an accessory right hepatic artery provided a territory more medial than a right hepatic artery coming from the proper right artery.

Risk factors associated with postoperative pain and discomfort in oculoplastic surgery with general anesthesia: a prospective study.

PURPOSE: To evaluate patient pain and discomfort following oculoplastic surgery performed under general anesthesia and to assess key factors associated with postoperative pain and discomfort. METHODS: A prospective observational cohort study was conducted among 212 consecutive patients who underwent oculoplastic surgery performed under general anesthesia. The patients were assessed according to quantified levels of pain and discomfort postoperatively. Analgesic requests were recorded, and responses were statistically analyzed. RESULTS: Pain and discomfort after oculoplastic surgery under general anesthesia were reported by 32.1% and 28.3% of the patients, respectively; 2.8% of the patients requested analgesic medication within 18 hours after surgery. The patients who underwent orbital decompression, secondary orbital implantation, and orbital fracture repair were more likely to develop significant postoperative pain and discomfort (P<0.001), and the patients who underwent enucleation/evisceration during orbital implantation were more likely to develop postoperative discomfort (P<0.001). The predictors of pain were smoking history, prior surgery on the operative eye, and anxiety (P<0.05), and the predictor of discomfort was anxiety (P<0.05). CONCLUSION: Patients undergoing oculoplastic surgery tend to experience postoperative pain and discomfort. Anxiety is a risk factor for both postoperative pain and discomfort, while smoking history and prior surgery on the operative eye may be associated with postoperative pain.

Sedation effects of intranasal dexmedetomidine delivered as sprays versus drops on pediatric response to venous cannulation.

OBJECTIVES: Mucosal atomization device (MAD) was designed to increase the bioavailability of intranasal medications by facilitating absorption, the present study aimed to evaluate and compare the sedation effects of intranasal dexmedetomidine delivered as drops versus sprays on pediatric responses to intravenous cannulation. METHODS: One hundred and six pediatric patients (aged from 2 to 5years) scheduled for elective ophthalmic surgery were intranasally received a dose of 2µg/kg in 20µl/kg of dexmedetomidine for sedation to reduce response to venous cannulation. The patients were randomized into syringe group and MAD group in which dexmedetomidine was delivered as drops or sprays via syringe or MAD respectively. The primary outcome was the response to peripheral vein cannulation assessed by the FLACC scores (faces, legs, activity, cry and consolability) 30min after intranasal administration of dexmedetomidine. The secondary outcomes included acceptance for intranasal medication, sedation onset time, and needle insertion times and any adverse event at the preoperative holding area. RESULTS: The FLACC scores in MAD group were significantly decreased than that treated by drops (P=0.021). The acceptance for intranasal administration between both groups was comparable (P>0.05), the onset time and the incidences in two and more times of needle insertion did not differ significantly between syringe and MAD groups (all P>0.05). None of patients were required to clinically intervene in heart rates reduction and none suffered respiratory depression after administrations of dexmedetomidine in either group. CONCLUSION: Intranasal dexmedetomidine by sprays offers better sedation effects to reduce responses to venous cannulation than drops.

Risk and association of HLA with oxcarbazepine-induced cutaneous adverse reactions in Asians.

OBJECTIVE: To investigate the risk and genetic association of oxcarbazepine-induced cutaneous adverse reactions (OXC-cADRs), including Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), in Asian populations (Chinese and Thai). METHODS: We prospectively enrolled patients with OXC-cADRs in Taiwan and Thailand from 2006 to 2014, and analyzed the clinical course, latent period, drug dosage, organ involvement, complications, and mortality. We also investigated the carrier rate of HLA-B*15:02 and HLA-A*31:01 of patients with OXC-cADRs and compared to OXC-tolerant controls. The incidence of OXC-SJS/TEN was compared with carbamazepine (CBZ)-induced SJS/TEN according to the nationwide population dataset from the Taiwan National Health Insurance Research Database. RESULTS: We enrolled 50 patients with OXC-cADRs, including 20 OXC-SJS/TEN and 6 drug reaction with eosinophilia and systemic symptoms, of Chinese patients from Taiwan and Thai patients from Thailand. OXC-cADRs presented with less clinical severity including limited skin detachment (all ≦5%) and no mortality. There was a significant association between HLA-B*15:02 and OXC-SJS (p = 1.87 × 10-10; odds ratio 27.90; 95% confidence interval [CI] 7.84-99.23) in Chinese and this significant association was also observed in Thai patients. The positive and negative predictive values of HLA-B*15:02 for OXC-SJS/TEN were 0.73% and 99.97%, respectively. HLA-A*31:01 was not associated with OXC-cADRs. The incidence and mortality of OXC-SJS/TEN was lower than CBZ-STS/TEN in new users (p = 0.003; relative risk 0.212; 95% CI 0.077-0.584). CONCLUSIONS: Our findings suggest that HLA-B*15:02 is significantly associated with OXC-SJS in Asian populations (Chinese and Thai). However, the severity and incidence of OXC-SJS/TEN are less than that of CBZ-SJS/TEN. The need for preemptive HLA-B*15:02 screening should be evaluated further.