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Background: In early breast cancer (EBC) patients, we aimed to determine whether circulating tumor DNA (ctDNA) analysis following primary surgery, before systemic therapy, identified molecular residual disease and was associated with risk of relapse and relapse-free survival (RFS)., Methods: Plasma was collected, retrospectively, before surgery, 1-14 weeks post-operatively, and before adjuvant therapy, and in a subset of patients after adjuvant therapy. A personalized, tumor-informed, multiplex PCR next generation sequencing assay (Signatera™) was used for ctDNA detection and quantification. The primary objective was to compare RFS and distant recurrence-free survival (DRFS) in patients with detected versus non-detected ctDNA., Results: A total of 48 patients with EBC (median age 50.5 years) [34 hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-), 5 HER2+, 9 triple-negative breast cancer) were included. ctDNA was detected in 64.5% (20/31) of patients before surgery, and 35.4% (17/48) after surgery. ctDNA detection before surgery was associated with tumor grade (P = 0.019), ctDNA detection after surgery was associated with receptor subtype (P = 0.01). Patients with ctDNA detected after surgery had worse DRFS [hazard ratio = 5.5, 95% confidence interval (CI) 1.1-28.5, P = 0.04]. RFS in patients with ctDNA detected after surgery was worse than in those with lack of ctDNA detection, although not statistically significant (hazard ratio = 3.7, 95% CI 0.9-15.7, P = 0.073). Patients with ctDNA detected preoperatively or post-operatively had a trend towards worse RFS (hazard ratio = 7.8, 95% CI 0.9-63.7, P = 0.05) and DRFS (hazard ratio = 6.8, 95% CI 0.8-57, P = 0.07) compared with those with ctDNA undetected at both timepoints. ctDNA detection anticipated clinical relapse with a median lead time of 16 months., Conclusions: In patients with treatment-naive EBC, ctDNA is detectable after surgery. The absence of ctDNA at a single post-surgical timepoint is associated with improved DRFS, supporting the development of future trials studying de-escalation of systemic therapy., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Molybdenum cofactor deficiency type A has successfully been treated in a small number of children with daily intravenous administration of cyclic pyranopterin monophosphate. Pharmacodynamic data for this novel treatment have not been published and alternative dosing intervals have not been explored. We monitored pharmacodynamic biomarkers of sulfite oxidase and xanthine oxidoreductase activity in three patients with MoCD-A for a period of 2 to 9 months after discontinuation of cPMP substitution. We found that the clinical and metabolic effects were sustained for longer than expected, over 7 days at least. Our data implicate a biological half-life of the molybdenum cofactor dependent enzyme activities of approximately 3 days and suggest the possibility that less frequent than once daily dosing intervals could be a safe alternative to current practice., Competing Interests: Declaration of competing interest BCS was principal investigator for clinical trials sponsored by Alexion Pharma International, and Origin Biosciences Inc. He reports a personal fee for attendance at an Advisory Board meeting and an unconditional educational grant from Origin Biosciences Inc. KB, HTW, AH, EE and VK have no conflict of interests to report. cPMP for the treatment of patients was provided free of charge on compassionate grounds from Colbourne Pharmaceuticals GmbH and Origin BioSciences Inc., respectively., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: To investigate the effects and clinical significance of NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome activated by interleukin (IL)-17A in chronic rhinosinusitis with nasal polyps (CRSwNP). Methods: Patients underwent nasal endoscopic surgery in the Third Affiliated Hospital of Sun Yat-sen University from January 2020 to December 2021 were collected, including 28 CRSwNP (including 19 males and 9 females, aged 19 to 67 years), 22 chronic rhinosinusitis without nasal polyps (CRSsNP) and 22 controls. qRT-PCR was used to detect the expressions of IL-17A, NLRP3, IL-1β and IL-18 in the three groups, and their correlations were analyzed. The positions of IL-17A, NLRP3 and IL-18 in nasal polys were analyzed by immunofluorescence. Western Blotting and ELISA were employed to detect the expression of NLRP3, IL-1β and IL-18 in the human nasal epithelial cells after using IL-17A stimulation or IL-17A receptor inhibitor. Immunofluorescence was used to observe the NLRP3, IL-1β, and IL-18 protein expression after IL-17A stimulating human nasal epithelial cells, and after the use of IL-17A receptor inhibitor and NLRP3 inhibitor MCC950. The correlations between NLRP3, IL-1β, IL-18 and CT scores, nasal endoscopic scores, visual analogue scale (VAS) scores, and sino-nasal outcome test (SNOT) 22 scores of CRSwNP patients were analyzed. SPSS 20.0 software was used for statistical analysis. Results: The expressions of IL-17A, NLRP3, IL-1β and IL-18 in the tissues of CRSwNP patients were significantly higher than those in CRSsNP group( P =0.018, P <0.001, P =0.005, P =0.016) and the control group(all P <0.001). IL-17A was positively correlated with the expression of NLRP3, IL-1β, and IL-18( r ralue was 0.643,0.650,0.629,respectively, all P <0.05). IL-17A, NLRP3, and IL-18 were co-localized in the epithelial propria of polyp tissue. IL-17A stimulated the expressions of NLRP3, IL-1β, and IL-18 in human nasal epithelial cells. After the use of IL-17A receptor inhibitor, the expressions of NLRP3, IL-1β, and IL-18 were significantly down-regulated. After the use of NLRP3 inhibitor MCC950, IL-17A was significantly down-regulated to promote the expression of NLRP3, IL-1β, and IL-18. The expressions of NLRP3, IL-1β and IL-18 were positively correlated with CT, nasal endoscopy, VAS, and SNOT22 scores in patients with CRSwNP. Conclusions: IL-17A promotes the release of IL-1β and IL-18 by activating the NLRP3 inflammasome and aggravates the severity of the disease in CRSwNP.

Objective: To establish a model of long-term free drinking mouse by feeding mice with alcohol to simulate the state of human voluntary long-term drinking, and on this basis, to further discuss the evaluation criteria of long-term free drinking mice model in sports, anxiety and cognitive behavior., Methods: Forty six-week-old SPF C57BL/6 male mouse were randomly divided into two groups: Long-term free drinking group ( n =20) and normal control group ( n =20). The two groups were given solid feed normally. The long-term free drinking group was free to take 10% alcohol and water every day, while the normal drinking group only took water every day. The mice were fed for 7 months, and were evaluated by a series of behavioral methods, including Rota-rod test, balance beam test, open filed test, the elevated plus maze, two-box social behavior, new object recognition, Y maze and water maze., Results: With the increase of drinking days, the mice showed significant alcohol addiction in the alcohol preference test. With the increase of alcohol intake, the mice in the long-term free choice drinking group had slightly shiny fur and reduced diet. Compared with the control group, the weight gain began to slow down from the third month, and the weight decreased significantly by the sixth and seventh months ( P =0.006, P < 0.001). The mice showed reduced balance locomotion ability ( P =0.003, P =0.001) in the rotary bar and balance beam test. In the open field and elevated cross test, the mice had obvious anxiety-like behavior ( P < 0.001). The mice showed decreased social ability in the two boxes of social behavior ( P < 0.016). In the experiment of new object recognition and Y maze, the exploration of new object decreased ( P =0.018, P =0.040). In the water maze, cognitive functions, such as learning and spatial memory were reduced ( P < 0.001)., Conclusion: The successful establishment of the long-term free drinking mouse model is more convenient for us to carry out further research on the neural mechanism of alcohol addiction, and lays an experimental foundation for exploring the neural mechanism of alcohol addiction and related new targets.

Objective: To preliminarily analyze the expression of angiotensin-converting enzyme 2 (ACE2) and to investigate its potential regulatory mechanism in chronic rhinosinusitis with nasal polyps (CRSwNP). Methods: Patients underwent nasal endoscopic surgery in the Third Affiliated Hospital of Sun Yat-sen University from February 2020 to May 2021 were selected, including 17 males and 6 females, aging from 23 to 66 years old. Expression of ACE2 was evaluated via immunohistochemical staining in controls with non-chronic rhinosinusitis, non-eosinophilic CRSwNP (non-ECRSwNP), and eosinophilic CRSwNP (ECRSwNP) tissue, respectively. Correlations between ACE2 and the indicated Th1/Th2-related cytokines (IFN-γ, IL-4, IL-5, IL-13, IL-25, IL-33, TSLP and periostin) were analyzed based on GSE72713 dataset. Protein-protein interaction (PPI) network was constructed via string database, immune infiltration of GSE72713 dataset was evaluated using cibersort algorithm. ACE2 was comprehensively analyzed by microRNA regulatory network, gene set enrichment analysis (GSEA) and pharmacological analysis. Statistical analysis was performed using GraphPad 7.0 and SPSS 20.0 software. Results: ACE2 was up-regulated in non-ECRSwNP compared with ECRSwNP. Microarray analysis showed that ACE2 was positively correlated with IFN-γ while inversely correlated with IL-5, IL-13 and periostin significantly. Analysis of immune infiltration suggested that ACE2 expression correlated positively with the number of M1 macrophage while negatively with M2 macrophage. GSEA demonstrated that interferon-related signaling pathways were up-regulated in non-ECRSwNP, and miRNA-200B/miRNA-200C/miRNA-429 pathways targeting ACE2 were enriched in ECRSwNP. Results of pharmacological analysis indicated that ampicillin was able to promote the expression of ACE2 whereas acetaminophen could down regulated the expression of ACE2. Conclusion: Expression pattern of ACE2 is varied in non-ECRSwNP and ECRSwNP, which may be related to the different infiltration of indicated cytokines and different regulatory pathways of miRNA.

Background: Pathologic complete response (pCR) to neoadjuvant chemotherapy (NAC) is strongly associated with favorable outcome. We examined the utility of serial circulating tumor DNA (ctDNA) testing for predicting pCR and risk of metastatic recurrence., Patients and Methods: Cell-free DNA (cfDNA) was isolated from 291 plasma samples of 84 high-risk early breast cancer patients treated in the neoadjuvant I-SPY 2 TRIAL with standard NAC alone or combined with MK-2206 (AKT inhibitor) treatment. Blood was collected at pretreatment (T0), 3 weeks after initiation of paclitaxel (T1), between paclitaxel and anthracycline regimens (T2), or prior to surgery (T3). A personalized ctDNA test was designed to detect up to 16 patient-specific mutations (from whole-exome sequencing of pretreatment tumor) in cfDNA by ultra-deep sequencing. The median follow-up time for survival analysis was 4.8 years., Results: At T0, 61 of 84 (73%) patients were ctDNA positive, which decreased over time (T1: 35%; T2: 14%; and T3: 9%). Patients who remained ctDNA positive at T1 were significantly more likely to have residual disease after NAC (83% non-pCR) compared with those who cleared ctDNA (52% non-pCR; odds ratio 4.33, P = 0.012). After NAC, all patients who achieved pCR were ctDNA negative (n = 17, 100%). For those who did not achieve pCR (n = 43), ctDNA-positive patients (14%) had a significantly increased risk of metastatic recurrence [hazard ratio (HR) 10.4; 95% confidence interval (CI) 2.3-46.6]; interestingly, patients who did not achieve pCR but were ctDNA negative (86%) had excellent outcome, similar to those who achieved pCR (HR 1.4; 95% CI 0.15-13.5)., Conclusions: Lack of ctDNA clearance was a significant predictor of poor response and metastatic recurrence, while clearance was associated with improved survival even in patients who did not achieve pCR. Personalized monitoring of ctDNA during NAC of high-risk early breast cancer may aid in real-time assessment of treatment response and help fine-tune pCR as a surrogate endpoint of survival., Competing Interests: Disclosure The following authors are employees of Natera, Inc. (HS, H-TW, RS, AT, SS, HP, PB, AA, ML, BZ). LJVV is co-founder, stockholder, and part-time employee of Agendia NV. The remaining authors have declared no conflicts of interest., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Purpose: For people with metabolic syndrome (MetS), altering the macronutrient composition of their diets might ameliorate metabolic abnormalities. The common method of clinical assessment only measures total lipid concentrations but ignores the individual species that contribute to these total concentrations. Thus, to predict the amelioration of MetS following caloric restriction (CR) and the intake of fish oil, we used lipidomics to investigate changes in plasma lipids and identify potential lipid metabolites., Methods: Lipidomics was performed using ultra-high-performance liquid chromatography-tandem mass spectrometry on plasma samples from a clinical trial conducted over 12 weeks. Subjects were randomized into two groups: CR (n = 12) and CR with fish oil (CRF, n = 9). Anthropometric and clinical parameters were measured and correlated with plasma lipidomics data., Results: Compared with baseline, significant differences were observed in body weight, waist circumference, blood pressure and interleukin-6 in both groups, but triglyceride (TG) levels significantly decreased in only the CRF group (all p < 0.05). A total of 138 lipid species were identified. Levels of species containing long-chain polyunsaturated fatty acids were significantly elevated-greater than twofold-following fish oil intake, these included TG (60:9) and phosphatidylcholine (p40:6) (all q < 0.05). TG (60:9) tended to correlate negatively with body weight, body mass index, blood pressure, and HbA1c following fish oil intake., Conclusion: CR and fish oil can ameliorate MetS features, including anthropometric parameters, blood pressure, and blood lipid concentrations. The levels of particular lipid species such as TG-containing docosapentaenoic acid were elevated post-intervention and negatively associated with MetS features. TG (60:9) may be proposed as a lipid metabolite to predict amelioration in MetS following the intake of CR and fish oil.

Objective: COVID-19 outbreak is still under global pandemic. China is facing the risks of importation and local rebound of COVID-19. Under the circumstances, preparations for medical resources are in urgently needed. Methods: Based on current understanding of the disease, we set up five scenarios and use the infectious disease transmission dynamic and pandemic theoretical static models to evaluate the demand for medical resources. Results: Different epidemic strength and strategies of disease control and prevention resulted in different levels of medical resource request, and active control strategy and effective measures could significantly decrease the requirement. During the epidemic rising phase, the cost of prevention and control measures and the requirement of professional response capacities would increase with potential high risk of medical resource demand sharply increasing. Conclusion: Regions with different economic level, population scale, and different prevention and control capabilities should all initiate scientific assessment of medical resource requirement under emergency response and prepare for possible future rebound and epidemic.

Objective: To explore the feasibility of clinical factors to predict the pathological complete response after neoadjuvant chemoradiotherapy in rectal cancer. Methods: A retrospective analysis was performed on clinical factors of 162 patients with rectal cancer, who underwent neoadjuvant chemoradiotherapy in the General Hospital of People's Liberation Army from January 2011 to December 2018.According to the postoperative pathological results, the patients were divided into pathological complete response (pCR) group and non-pathological complete response group (non-pCR group) to check the predictive clinical factors for pCR. Results: Twenty-eight cases achieved pCR after neoadjuvant chemoradiation (17.3%, 28/162). Univariate analysis showed that patients with higher differentiation ( P= 0.024), tumor occupation of the bowel lume n ≤1/2 ( P= 0.006), earlier clinical T stage ( P= 0.013), earlier clinical N stage ( P= 0.009), the time interval between neoadjuvant chemoradiotherapy and surgery>49 days ( P= 0.006), and maximum tumor diamete r ≤5 cm ( P= 0.019) were more likely to obtain pCR, and the differences werestatistically significant. Multivariate analysis showed that tumor occupation of the bowel lume n ≤1/2 ( P= 0.01), maximum tumor diamete r ≤5 cm ( P= 0.035), and the interval>49 days ( P= 0.009) were independent factors in predicting pCR after neoadjuvant therapy. Conclusion: Tumor occupation of the bowel lumen, maximum tumor diameter, and the time interval between neoadjuvant chemoradiotherapy and surgery can predict the pCR in rectal cancer.

Objective: To explore changing trend in prognosis of primary hypopharyngeal carcinoma and to analyze the reasons at the Eye, Ear, Nose and Throat Hospital of Fudan University. Methods: We retrospectively analyzed the clinical data of 461 patients with primary hypopharyngeal carcinoma treated at the Eye, Ear, Nose and Throat Hospital of Fudan University from 2003 to 2007 (Group 1) and 2010 to 2014 (Group 2) according to the inclusion criteria. 142 from Group 1, including 133 males and 9 females, rangedfrom 38 to 82 years old and 319 from Group 2, including 313 males and 6 females, ranged from 39 to 81 years old, were included in this work. The laryngeal function preservation rate, survival outcome, application and effect of pre-and post-operative adjuvant therapy were compared. SPSS 24.0 was used for statistical analyses. Results: There were 62 patients with early disease (T1-2N0) including 18 in Group 1 and 44 in Group 2, in whom 3 (16.7%) underwent surgical procedures with laryngeal function preservation in Group 1, while, 30 (68.2%) underwent laryngeal function preservation surgery in Group 2. The laryngeal function preservation rate showed an obviously upward trend in recent years (χ(2)=13.617, P< 0.001), whereas, the recurrence-free survival rate (RFS) and overall survival rate (OS) showed no significant differences between two groups ( P= 0.469 and 0.808, respectively). Among the 399 patients with advanced disease, 124 were in Group 1 and 275 in Group 2. After propensity score matching (PSM) was used, the OS rate was significantly higher for Group 2 than Group 1 ( P= 0.017), while the application of laryngeal function preservation surgery was significantly higher in Group 2 (χ(2)=4.686, P= 0.030). The application rates of preoperative adjuvant therapy and postoperative adjuvant chemotherapy were significantly higher in group 2 than in group 1 (χ(2)=5.687, P= 0.017; χ(2)=19.407, P< 0.001). Conclusion: The application of laryngeal function preserving surgery significantly increases the retention rate of laryngeal functions in patients with early-stage hypopharyngeal carcinoma, with similar long-term survival outcomes. The application of comprehensive treatment including preoperative adjuvant therapy and postoperative adjuvant treatments, especially postoperative chemoradiotherapy, shows an obvious increase in the function preservation rate and long-term survival in patients with advanced hypopharyngeal carcinoma.

Purpose: Prenatal stress (PS) during pregnancy affects in utero- and postnatal child brain-development. Key systems affected are the hypothalamic-pituitary-adrenal axis and the autonomic nervous system (ANS). Maternal- and fetal ANS activity can be gauged non-invasively from transabdominal electrocardiogram (taECG). We propose a novel approach to assess couplings between maternal (mHR) and fetal heart rate (fHR) as a new biomarker for PS based on bivariate phase-rectified signal averaging (BPRSA). We hypothesized that PS exerts lasting impact on fHR., Methods: Prospective case-control study matched for maternal age, parity, and gestational age during the third trimester using the Cohen Perceived Stress Scale (PSS-10) questionnaire with PSS-10 over or equal 19 classified as stress group (SG). Women with PSS-10 < 19 served as control group (CG). Fetal electrocardiograms were recorded by a taECG. Coupling between mHR and fHR was analyzed by BPRSA resulting in fetal stress index (FSI). Maternal hair cortisol, a memory of chronic stress exposure for 2-3 months, was measured at birth., Results: 538/1500 pregnant women returned the questionnaire, 55/538 (10.2%) mother-child pairs formed SG and were matched with 55/449 (12.2%) consecutive patients as CG. Maternal hair cortisol was 86.6 (48.0-169.2) versus 53.0 (34.4-105.9) pg/mg (p = 0.029). At 36 + 5 weeks, FSI was significantly higher in fetuses of stressed mothers when compared to controls [0.43 (0.18-0.85) versus 0.00 (- 0.49-0.18), p < 0.001]., Conclusion: Prenatal maternal stress affects the coupling between maternal and fetal heart rate detectable non-invasively a month prior to birth. Lasting effects on neurodevelopment of affected offspring should be studied., Trial Registration: Clinical trial registration: NCT03389178.

Objective: To determine the relationship between nodal disease distribution patterns and oncological outcome and optimum management of cN0/cN1 patients with hypopharyngeal squamous cell carcinoma (HPSCC). Methods: The collected clinical data and the follow-up disease-free survival (DFS) information from 154 patients with HPSCC treated between 2001 and 2014 in Eye Ear Nose and Throat Hospital of Fudan University were retrospectively analyzed. Kaplan-Meier method was used to calculate DFS rate. Log-rank test and Cox regression model were performed to evaluate the survival prognostic factors for univariate and multivariate analyses. Results: Among 154 patients (63 cN0 patients, 91 cN1 patients) with HPSCC,in whom 148 were male, 6 were female, with an arerage age of (58.6±9.9), 63 cN0 patients received lateral neck dissection, of whom 9 were histologically positive nodes. Particularly, occult metastasis rate was 15.6%(7/45) for HPSCC in pyriform sinus and 18.2%(2/11) for HPSCC in posterior pharyngeal wall. Among 91 cN1 HPSCC, 34 underwent radical neck dissection and 54 underwent selective neck dissection. DFS for patients(T3-4N1) with radical neck dissection was lower than that for patient with selective neck dissection(15.2% vs.39.5%, χ(2)=5.153, P <0.05). The DFS of cN0 HPSCC was overestimated by the false-negative patients (cN0→pN+) for cN0 HPSCC and the DFS of cN1 HPSCC was underestimated by the false-positive(cN1→pN0) for cN1 HPSCC. Conclusions: For cN1 HPSCC, compared with radical neck dissection, selective neck dissection may be considered as a more adequate method for removal of metastatic lymph nodes. Postoperative combined therapy and follow-up strategy should be established according to pathological N staging.

Objective: To investigate the effectiveness of endoscopic keel placement for the prevention and treatment of bilateral vocal cord adhesion. Method: There are 47 cases with bilateral vocal cord lesions and 38 cases with laryngeal adhesion in this study. Bilateral vocal cord lesions were removed and laryngeal adhesion was cut and divided. Afterwards, a silicone keel was placed in each case using a Lichtenberger endo-extralaryngeal needle carrier. The keel was removed 4 weeks post-surgery and the vocal cords were observed using a laryngoscopy monthly. Result: During the 1-year follow-up, 39 (83.0%) cases with bilateral vocal cord lesions and 28(73.7%) cases with laryngeal adhesion did not develop laryngeal webs. A pseudomembrane covering the vocal cords was observed at the time of keel removal in 16 cases of all. Unfortunately, 15 cases (93.75%) developed laryngeal webs among them. However, in the cases without a pseudomembrane, only 3 (4.35%) cases formed glottic webs post-surgery( P <0.01). Conclusion: Endoscopic keel placement is an effective method for the prevention and treatment of bilateral vocal cord adhesion. The pseudomembrane detected at the time of keel removal is probably a risk factor for the development of glottic webs., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)

Objective: To investigate the risks of pre-pregnancy overweight, excessive gestational weight gain on macrosomia. Methods: We conducted one hospital-based cohort study, focusing on pregnant women from January 2015. All pregnant women attending to this hospital for maternal check-ups, were included in our cohort and followed to the time of delivery. Data related to general demographic characteristics, pregnancy and health status of those pregnant women, was collected and maternal pre-pregnant BMI and maternal weight gain were calculated. Logistic regression was used to explore the risk difference of pre-pregnancy BMI, excessive gestational weight gain on macrosomia. Results: The overall incidence of macrosomia in our cohort appeared as 6.6% (149/2 243). After adjusting the confounding factors including age and histories on pregnancy, pre-pregnancy overweight/obesity was associated with higher risks of macrosomia ( OR =3.12, 95 %CI : 1.35-7.22, P =0.008; OR =2.99, 95 %CI : 1.17-7.63, P =0.022) when comparing to those with normal pre-pregnancy weight. Cesarean delivery and sex of the offspring were associated with higher risk of macrosomia, while excessive gestational weight gain showed no significant difference ( OR =1.41, 95 %CI : 0.96-2.09, P =0.084). Our data showed that Macrosomia was statistically associated with gestational weight gain ( P =0.002). After controlling parameters as age, history of pregnancy and related complications of the pregnant women, results from the logistic regression showed that women with gestational inadequate weight gain having reduced risks to deliver macrosomia, when compared to those pregnant women with adequate weight gain ( OR =0.52, 95 %CI : 0.30-0.90, P =0.019). Conclusion: Pre-pregnancy overweight and obesity were on higher risks to macrosomia.

Objective: To explore the association between the morphological classification and prognosis of conservative treatment for vocal fold leukoplakia. Method: Patients with different types of vocal fold leukoplakia received conservative treatment first. Those who had failed response to conservative treatment or recurred received carbon dioxide laser resection. Then the efficacy and recurrence rate were compared among the three types of vocal fold leukoplakia. Result: Two hundred and thirty-six patients consisted of 78 flat and smooth cases, 146 bulge and smooth cases, and 12 rough cases. The complete response rate of conservative treatment for the three types was 80.8%, 65.1%, and 0%, respectively ( P <0.01). Out of 158 patients who had complete response to conservative treatment, 10.1% cases recurred in 1 year (flat and smooth vs. bulge and smooth, 6.3% vs. 12.6%, P =0.283). Totally, 78 patients had no complete response to conservative treatment and 16 patients experienced recurrence, whose complete response rate of carbon dioxide resection was 89.5%, 85.7%, and 75.0%, respectively ( P =0.53). The pathological results were significantly different among three types. The complete response rate of conservative treatment combined with surgery for three types was 97.4%, 93.8%, and 75.0%, respectively, and the complete response rate of flat and smooth type was significantly higher than that of rough type ( P =0.002). Conclusion: The Conservative treatment could be based on the morphological classification of vocal fold leukoplakia. The treatment modality that conservative treatment combined with surgery had no impact on the prognosis of vocal fold leukoplakia., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)

Objective: To investigate work-related musculoskeletal disorders (WMSDs) of workover workers in an oilfield and explore the influencing factors. Methods: In June 2016, 685 workover workers were selected as working group, and 191 other workers exposed to toxic and harmful operations were selected as control group. Cross sectional investigation was conducted by self-made questionnaire, and the influencing factors of musculoskeletal disorders were analyzed by unconditional multivariate Logistic regression. Results: The total annual prevalence of WMSDs for workover workers was 90.5%, with the highest prevalence of low back pain of 71.5%. The prevalence of WMSDs increased with the increase of service age, and the difference between the drinkers was higher than that of the non drinkers ( P <0.05) . Multivariate Logistic regression analysis showed that working age, drinking and the posture of lifting heavy objects were risk factors for WMSDs in workover workers. Conclusion: The WMSDs appears to be a serious problem in oilfield workover workers. Corresponding measures should be taken to prevent the risk factors and control the occurrence of diseases effectively.

Objective: To explore the fundamental clinical characteristics and survival prognostic factors of laryngeal squamous cell carcinoma (LSCC) patients treated with open laryngeal function-preserving operations. Method: The collected clinical data and the follow-up survival information from 760 patients with LSCC undergoing open laryngeal function-preserving operations between January 2005 and December 2010 in Eye & ENT Hospital of Fudan University were retrospectively analyzed. Kaplan-Meier was applied to calculate survival rates. Log-rank test and Cox regression model were performed to evaluate the survival prognostic factors for univariate and multivariate analysis. Result: Among the enrolled 760 cases, 697 patients were glottic cancer, followed by 59 cases in supraglottis and 4 cases in subglottis. The number of laryngeal cancer patients staged in T1 to T4 was 222, 420, 112 and 6, respectively. 27 patients had positive cervical lymph nodes. There were 220, 408, 111 and 21 patients with clinical stage Ⅰ to Ⅳ, respectively. The 5-year overall survival (OS), disease free survival (DFS) and disease specific survival (DSS) rates were 89.3%, 83.9% and 89.8%, respectively. Multivariate Cox analysis indicated that clinical stage and second primary tumor were independent influencing factors for the OS rate, while, age, primary site, pathological differentiation, T stage, clinical stage and surgical margin were independent risk factors for tumor recurrence and progression ( P <0.05). Conclusion: Open laryngeal function-preserving operation is a crucial therapeutic strategy applicable to LSCC patients in early and selected advanced stage in China. Early diagnosis and therapy, and sufficient safety surgical margin are keys for improving the survival rate and reducing the risk of relapse for laryngeal cancer patients.

Objective: The utility of fetal heart rate (FHR) monitoring can only be achieved with an acquisition sampling rate that preserves the underlying physiological information on the millisecond time scale (1000 Hz rather than 4 Hz). For such acquisition, fetal ECG (fECG) is required, rather than the ultrasound to derive FHR. We tested one recently developed algorithm, SAVER, and two widely applied algorithms to extract fECG from a single-channel maternal ECG signal recorded over the xyphoid process rather than the routine abdominal signal., Approach: At 126dG, ECG was attached to near-term ewe and fetal shoulders, manubrium and xyphoid processes (n  =  12). fECG served as the ground-truth to which the fetal ECG signal extracted from the simultaneously-acquired maternal ECG was compared. All fetuses were in good health during surgery (pH 7.29  ±  0.03, pO 2 33.2  ±  8.4, pCO 2 56.0  ±  7.8, O 2 Sat 78.3  ±  7.6, lactate 2.8  ±  0.6, BE  -0.3  ±  2.4)., Main Result: In all animals, single lead fECG extraction algorithm could not extract fECG from the maternal ECG signal over the xyphoid process with the F1 less than 50%., Significance: The applied fECG extraction algorithms might be unsuitable for the maternal ECG signal over the xyphoid process, or the latter does not contain strong enough fECG signal, although the lead is near the mother's abdomen. Fetal sheep model is widely used to mimic various fetal conditions, yet ECG recordings in a public data set form are not available to test the predictive ability of fECG and FHR. We are making this data set openly available to other researchers to foster non-invasive fECG acquisition in this animal model.

Objective: To evaluate the oncologic and functional outcomes of supracricoid partial laryngectomy (SCPL) in the treatment of laryngeal carcinoma. Methods: A total of 298 laryngeal carcinoma patients who underwent SCPL treatment from January 2005 to December 2013 were reviewed retrospectively. Clinical data of demographic and clinical characteristics, postoperative complications, rehabilitation information, recurrence and metastasis were analysed. Survival and local control were used to evaluate the clinical outcome.Data were analyzed by SPSS 23.0 software. Results: Thirty-one patients with supraglottic carcinoma underwent cricohyoidoepiglottopexy (CHEP)and 267 with glottic carcinoma underwent cricohyoidopexy (CHP) were enrolled in this study. The mean duration of followed up was 74 months, ranging from 12 to 146 months. Fifty-four cases died at last follow-up. With respect to 31 patients with supraglottic carcinoma, 5- and 10-year overall survival rates and disease specific survival rates all were 78.1%; 5- and 10-year disease free survival rates were 72.1% and 63.7% respectively; and 5- and 10-year local control rates were both 84.2%. In 267 patients with glottic carcinoma, 5- and 10-year overall survival rates were 85.8% and 77.1% respectively; 5- and 10-year disease specific survival rates were 86.6% and 78.4% respectively; 5- and 10-year disease free survival rates were 80.6% and 74.2% respectively; and 5- and 10-year local control rates were 90.0% and 89.4% respectively. The survival rate of patients with glottic carcinoma at stage T1 was higher than that at stage T2 or T3, and the disease free survival rate of patients with early stage was superior than that of patients with advance stage. Cox regression analysis showed that tumor stage T2, and T3, tumor recurrence, and tumor metastasis were independent risk factors for survival. Furthermore, nasogastric feeding tube removal rate was 100% and the decannulation rates of SCPL were 96% in the patients with SCPL. Conclusions: SCPL is a safe procedure with tumor resection for laryngeal carcinoma, with preserving of swallowing, respiration, and phonation functions, and has excellent survival and local control rates. This procedure could be considered as a standard function-sparing treatment for selected patients with laryngeal carcinoma of stages T1b-T3.

Objective: To summarize the clinical features of patients with ovarian tumor and anti-N-methyl-D-aspartate receptor(NMDAR) encephalitis, and to explore the influence of operation patterns on the prognosis. Methods: The clinical information of patients with ovarian tumor and anti-NMDAR encephalitis in The 3rd Affiliated Hospital of Sun Yat-Sen University and The Zhujiang Hospital of Southern Medical University were collected and analyzed. Results: There were 15 patients were enrolled in this study, with the average age of 24.5±5.0 years old. The most frequent first symptom was psychosis. The main clinical features were psychosis, seizures, conscious disturbance, autonomic dysfunction, dyskinesia, central hypoventilation and impaired memory. Most patients' symptoms were relieved after immunotherapy and surgery. The number of favorable prognosis of patients (mRS score 0-2) with ovariectomy was higher than that of the patients with ovarian cystectomy (5 vs 3). But the difference had no statistical significance ( P =0.529). Conclusions: For young female patients with psychosis, we should be alert to the possibility of anti-NMDAR encephalitis and screen for tumor. Treated with immunotherapy and operation, most patients can get a favorable prognosis.

Neurotrophins particularly brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) are crucial modulators in the neurodevelopment and maintenance of central and peripheral nervous systems. Neurotrophin hypothesis of schizophrenia (SCZ) postulated that the changes in the brains of SCZ patients are the result of disturbances of developing processes involving neurotrophic factors. This hypothesis was mainly supported by the abnormal regulation of BDNF in SCZ, especially the decreased peripheral blood BDNF levels in SCZ patients validated by several meta-analyses. However, the regulation of NGF in SCZ remains unclear because of the inconsistent findings from the clinical studies. Therefore, we undertook, to the best of our knowledge, the first systematic review with a meta-analysis to quantitatively summarize the peripheral blood NGF data in SCZ patients compared with healthy control (HC) subjects. A systematic search of Pubmed, PsycINFO and Web of Science identified 13 articles encompassing a sample of 1693 individuals for the meta-analysis. Random-effects meta-analysis showed that patients with SCZ had significantly decreased peripheral blood levels of NGF when compared with the HC subjects (Hedges's g=-0.633, 95% confidence interval (CI)=-0.948 to -0.318, P<0.001). Subgroup analyses revealed reduced NGF levels both in serum (Hedges's g=-0.671, 95% CI=-1.259 to -0.084, P=0.025) and plasma (Hedges's g=-0.621, 95% CI=-0.980 to -0.261, P<0.001) of the patients, and in drug-free (Hedges's g=-0.670, 95% CI=-1.118 to -0.222, P=0.003) and medicated (Hedges's g=-0.357, 95% CI=-0.592 to -0.123, P=0.003) patients with SCZ. Furthermore, meta-regression analyses showed that age, gender and sample size had no moderating effects on the outcome of the meta-analysis, whereas disease severity might be a confounding factor for the meta-analysis. These results demonstrated that patients with SCZ are accompanied by the decreased peripheral blood NGF levels, strengthening the clinical evidence of an abnormal neurotrophin profile in the patients with SCZ.

Background: Mutations in the DNAJB6 gene have been identified as a rare cause of dominantly inherited limb-girdle muscular dystrophy or distal-onset myopathy., Materials and Methods: Exome sequencing was performed to investigate a Taiwanese family with a dominantly inherited distal-onset myopathy. Functional effects of the causal mutation were investigated in vitro., Results: Exome sequencing of the two affected individuals in this family identified a heterozygous mutation, c.287C>T (p.Pro96Leu) in the DNAJB6 gene, which co-segregated with the myopathy within all 12 family members. Notably, this mutation is novel and localizes within the glycine and phenylalanine-rich (G/F) domain and alters an amino acid residue previously reported with a different mutation. Furthermore, immunofluorescence analyses and filter trap assay demonstrated that the c.287C>T (p.Pro96Leu) mutation possessed a dominant negative effect on the anti-aggregation function of DNAJB6 protein., Conclusion: This study expands the molecular spectrum of DNAJB6 mutations and also emphasizes the pathogenic role of DNAJB6 dysfunction in distal-onset myopathy., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: To explore the reconstruction methods of oropharyngeal defects after resection of tonsillar cancer by mandibular swing approach. Method: Twenty four cases of patients with tonsillar carcinoma hospitalized in our institution from January, 2010 to December, 2015 were analyzed. Based on the degree and extent of tissue defects, they were divided into three categories.①Small defects, including loss of tonsillar fossa and pharyngeal arches; ②Moderate defects, including small defects of soft palate or tongue root besides lateropharyngeal defects; ③Large defects, including large defects of soft palate and tongue root besides lateropharyngeal defects. The tissue defects of 8 patients belonged to small defects, of whom 4 cases were repaired with mid-thick skin and the others were restored by radial forearm flaps. There were 5 cases of patients with moderate oropharyngeal defects after surgery of tonsillar carcinoma. These defects were reconstructed by radial forearm flaps(2 cases) and anterolateral femoral skin flaps (3 cases) respectively, while the remaining large defects of 11 patients were renovated using pectoralis major myocutaneous flaps(9 cases) and anterolateral femoral skin flaps(2 cases). Result: All the patients healed by first intention after surgery.Four transplanted skin grafts on the regions of small defects survived completely.5 cases of radial forearm flaps and anterolateral femoral skin flaps also survived well, whereas only one radial forearm flap suffered from vascular crisis leading to failure at 5 days postoperatively. The necrotic flaps were then removed by submaxillary space and oral cavity and the wounds were self-healed. The tissue defects were successfully repaired by pectoralis major myocutaneous flaps. Although the surgical wounds swelled, they were obviously relieved half a year later. In the tonsillar cancer patients encroached on soft palates, one occurred nasopharyngeal reflux and 3 spoke vaguely but understandably. The other patients' function of chewing, deglutition, respiration and speech were restored well. Conclusion: Small defects after resection by mandibular swing approach could be repaired by mid-thick skin or radial forearm flaps. Moderate defects of T3 tonsillar cancer could be restored using radial forearm flaps or anterolateral femoral skin flaps, while anterolateral femoral skin flaps or pectoralis major myocutaneous flaps could reconstructed the large defects of T3 or T4 tonsillar cancer., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)

Objective: To investigate the clinical value of acoustic radiation force impulse (ARFI)technique in predicting esophageal and gastric varices in patients with biliary atresia after Kasai portoenterostomy. Methods: A total of 42 patients with biliary atresia after Kasai portoenterostomy were collected from September 2015 to May 2016 in Tianjin First Central Hospital.ARFI technique was used to measure the stiffness of liver and spleen, and 28 healthy children as control.According to the result of CT examination , patients with biliary atresia were divided into two groups , twenty-three patients with esophageal and gastric varices(A group) and nineteen patients without esophageal and gastric varices (B group), Comparing the difference of liver and spleen stiffness between the two groups.The ROC curve analysis was carried out to test the diagnostic power of effective parameter. Results: The ARFI value of liver (2.98±0.80) m/s and spleen (3.00±0.33) m/s of patients with biliary atresia was significantly higher than that of control group((1.10±0.16) m/s, (2.12±0.32) m/s), the differences had statistical significance (both P <0.01). Between group A and group B, the spleen ARFI value of group A(3.16±0.26) m/s was higher than group B(2.83±0.32) m/s, the difference had statistical significance ( P <0.01), whereas there was no statistical difference of liver ARFI value between two group((2.93±0.65), (3.02±0.96) m/s)( P >0.05). The cut-off ARFI value of spleen to diagnose esophageal and gastric varices in biliary atresia was 3.02 m/s, and the biggest area under the ROC curve, sensitivity, and specificity were 0.81, 78.6% and 84.5%, respectively. Conclusion: ARFI can be used as a noninvasive method to predict the presence of esophageal and gastric varices in patients with biliary atresia after Kasai portoenterostomy.

Head and neck squamous cell carcinoma(HNSCC) is the sixth most common malignancies of human beings. The prognosis of advanced HNSCC is poor despite improvements in traditional treatment strategies including surgery, chemotherapy, and radiotherapy. Cancer immunotherapy is the use of the immune system to treat cancer, which provides a sustained antitumor reaction but an absense of chemoresistance. Cancer immunotherapy is becoming the forth treatment strategy towards cancer. Therefore, we reviewed the current state of immunotherapy for HNSCC.

What Is Known and Objectives: Choosing an alternative statin is recommended when managing statin-associated muscle symptoms (SAMS) and new hydrophilic statins are often suggested. We report on a case of statin-associated muscle damage that was successfully managed by simplifying the patient's combination therapy with simvastatin-ezetimibe to simvastatin alone., Case Summary: The patient experienced SAMS when he was successively treated with atorvastatin, rosuvastatin, Xuezhikang capsule and combined simvastatin/ezetimibe therapy. However, the patient tolerated simvastatin therapy well even at a dose of 40 mg/day., What Is New and Conclusion: Our case suggests that patients with SAMS who are intolerant to a wide variety of statins may be successfully managed with simvastatin monotherapy., (© 2016 John Wiley & Sons Ltd.)

Objective: The aim of this study is to investigate the clinical and pathological features of vocal cord polyp. Method: Retrospective analyzed the clinical and pathological data of 1116 cases in vocal cord polyp patients treated with suspension microlaryngoscopic surgery. Result: The bradycardia was observed in 170 cases(15.2%) during the suspension of laryngoscope under general anesthesia. In this case，the suspension was stopped or the laryngoscope was taken out of mouth and atropine was administrated by intravenous injection. After that, heartbeat gradually accelerated and approached to normal,then the suspension was begun again to complete microlaryngoscopic surgery. Among the 1116 cases,1094(98%) were cured,22(2%) were improved，and no case was invalid. No pharyngeal injury was in 865 cases(77.5%). Mild,moderate and severe palatoglossal arch injury was observed in 139 (12.5%)cases，86(7.7%)cases,and 26 (2.3%) cases，respectively. The incidences of epithelial hyperplasia and dysplasia in vocal cord polyp were 35.3% and 5.0%, respectively. The prevalence rates of epithelial hyperplasia and dysplasia in male and female patients of vocal cord polyp were 76.2%,23.8% ( P <0.01) and 78.6%,21.4% ( P <0.01),respectively. And the prevalence rates of keratinization and parakeratosis in male and female patients were 93.1%,6.9% ( P <0.01) and 93.1%,6.9% ( P <0.01),respectively.The incidence of keratinization in patients of no epithelial hyperplasia, epithelial hyperplasia and epithelial dysplasia were 2.1%,18.2% and 30.3%,respectively，with significant difference in pairwise comparison. Conclusion: High incidence of vocal cord polyp is at the age from 31 to 60 years old.Although laryngomicrosurgery is an effective treatment for vocal cord polyp, pharyngeal injury and laryngopharyngeal vagal reflex should be noticed during the operation.In addition,vocal cord polyps in male patients are susceptible to epithelial dysplasia and keratinization., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)

Background: This work was to evaluate the efficacy and safety of cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) with lobaplatin and docetaxel to treat peritoneal carcinomatosis (PC) from gastric cancer (GC)., Methods: A total of 50 consecutive GC PC patients treated by 52 CRS+HIPEC procedures with lobaplatin 50 mg/m(2) and docetaxel 60 mg/m(2) in 6000 mL of normal saline at (43 ± 0.5) °C for 60 min. The primary endpoint was overall survival (OS), and the secondary endpoints were perioperative safety profiles., Results: At the median follow-up of 22.5 (range, 5.1-50.7) months, the median OS was 14.3 (95% CI 7.6-21.0) months, and the 1-, 2-, and 3-year survival rates were 58%, 40%, and 32%, respectively. Mortality and serious adverse event (grade 3-5) morbidity rates in postoperative 30 days were 0.0% and 23.1%, respectively. Univariate analysis identified 4 parameters with significant effects on OS: completeness of cytoreduction (CC) 0-1, normal (N) the preoperative tumor markers level (TM), adjuvant chemotherapy ≥6 cycles, and peritoneal cancer index ≤20. However, multivariate analysis identified CC0-1, perioperative TM (N), adjuvant chemotherapy ≥6 cycles as the independent predictor for better survival., Conclusions: CRS+HIPEC with lobaplatin and docetaxel to treat selected GC PC could improve OS, with acceptable perioperative safety., (Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objective: To investigate the clinical characteristics, surgical treatment outcomes and prognostic factors of hypopharyngeal carcinoma., Methods: A retrospective review of the Eye & ENT Hospital of Fudan University patients' database between January 2003 and June 2013 was conducted and a total of 386 patients were enrolled in the study. Patients' clinical and oncological information was collected and survival rates were analyzed using Kaplan-Meier curves. Prognostic factors were evaluated with multivariate Cox model survival analysis., Results: Among the 386 patients 95.9% were males and 4.1% were females, with an average age of (58.4±9.4) years. The primary tumor sites were pyriform sinus (76.7%), posterior hypopharyngeal wall (17.3%) and postcricoid region (6.0%). There were 31(8.0%), 83(21.5%), 175(45.3%) and 97(25.1%) patients with stage T1 to T4, respectively, 99(25.6%), 74(19.2%), 181(46.9%) and 32(8.3%) patients with stage N0 to N3, respectively , and 3 patients with distant metastasis to lung on initial diagnosis. Second primary cancers were found in 28 cases (7.3%). The 5-year overall survival (OS), disease specific survival (DSS) and disease free survival (DFS) were 45.8%, 48.1% and 46.0% respectively according to Kaplan-Meier survival curves. Multivariate Cox regression model showed significant association between 5-year overall survival rate and T stage (P<0.001), N stage (P=0.003) and second primary tumors (P=0.017). Advanced T stage and lymphovascular invasion were associated with a higher rate of recurrence (P<0.001)., Conclusions: Hypopharyngeal squamous cell carcinoma has a dismal prognosis, with high rates of submucosal infiltration, cervical lymph node metastasis and distant metastasis. Treatment choices should be made according to TNM stage and overall health conditions in order to achieve ideal oncologic and functional results. Surgery with postoperative chemoradiation therapy is the main treatment for advanced-stage hypopharyngeal cancer.

Objective: To evaluate the efficacy and economics of sublingual immunotherapy (SLIT) with Dermatophagoides farinae drops in patients with allergic rhinitis and allergic asthma. Method: Two hundred and three patients (aged 4-60 yr) with allergic rhinitis and allergic asthma induced by house dust mites were retrospectively analyzed. Eighty-six patients were treated by SLIT with standardized Dermatophagoides farina drops and pharmacotherapy (SLIT group), while 117 patients were treated by standardized pharmacotherapy (drug group). Patients were followed up for 2 years with one visit in every 3 months. Total nasal syptom score (TNSS), total rhinitis medicine score (TRMS), daytime asthma syptom score (DASS), nighttime asthma syptom score (NASS), total asthma medicine score (TAMS) and treatment charge were recorded at each visit. Result: There was no significant difference between two groups in TNSS, TRMS, DASS, NASS, TAMS before treatment (all P >0.05). After 1-year or 2-year duration, there were significant differences between the SLIT group and drug group in TNSS, TMSS, DASS, NASS, TAMS (all P <0.01). After 1-year or 2-year duration, the symptom scores and medication scores of SLIT group significantly decreased compared with those before treatment (all P <0.01). In terms of treatment charge, although direct cost of SLIT group was a little higher than that of drug group, the indirect cost of SLIT group was remarkably lower than that of drug group, showing significant difference ( P <0.01). Conclusion: SLIT with Dermatophagoides farinae drops is effective in patients with allergic rhinitis and allergic asthma, which may also reduce indirect cost., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)

Analysis of Permian-Triassic brachiopod diversity and body size changes from different water depths spanning the continental shelf to basinal facies in South China provides insights into the process of environmental deterioration. Comparison of the temporal changes of brachiopod diversity between deepwater and shallow-water facies demonstrates that deepwater brachiopods disappeared earlier than shallow-water brachiopods. This indicates that high environmental stress commenced first in deepwater settings and later extended to shallow waters. This environmental stress is attributed to major volcanic eruptions, which first led to formation of a stratified ocean and a chemocline in the outer shelf and deeper water environments, causing the disappearance of deep marine benthos including brachiopods. The chemocline then rapidly migrated upward and extended to shallow waters, causing widespread mass extinction of shallow marine benthos. We predict that the spatial and temporal patterns of earlier onset of disappearance/extinction and ecological crisis in deeper water ecosystems will be recorded during other episodes of rapid global warming., (© 2014 John Wiley & Sons Ltd.)

Aim: To evaluate the feasibility of a low-dose contrast medium protocol for 64-detector row computed tomography angiography (CTA) of the neck using a low-tube-voltage/high-tube-current setting., Materials and Methods: A phantom study was performed using 64-detector row spiral CT at multiple tube voltage and current settings. Iodine contrast medium attenuation curves were acquired by processing and used to select the best contrast medium-to-noise ratio (CNR). A prospective clinical study was then performed on 84 patients requiring neck CTA. Patients were randomly divided into two groups of 42. Group A was examined using the conventional imaging protocol (120 kV, 400 mAs) and group B was examined at 80 kV and 600 mAs along with a 50% reduction in contrast medium dose. The CT dose index-volume (CTDI(vol)), background noise (BN), and CNR were measured and statistically analysed. Various image quality criteria were evaluated by two senior radiologists using a qualitative five-point scale., Results: Comparing group B with A, CTDIvol decreased by 54% (B: 27.48 mGy, A: 59.11 mGy), however, the CNR increased by 50%. The mean attenuation, which was caused by venous streak artefacts, was significantly lower in group B than A. Qualitative image analysis found that all criteria were significantly better for group B than A., Conclusion: At 64-detector row spiral CT, the low-tube-voltage/high-tube-current with low-dose contrast medium protocol was superior to the conventional protocol regarding radiation dose, venous streak artefacts, and image quality, and is feasible for CTA of the neck., (Copyright © 2013 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Background: Heart rate variability (HRV) may reflect various physiological dynamics. In particular, variation of R-R peak interval (RRI) of electrocardiography appears regularly oscillatory in deeper levels of anaesthesia and less regular in lighter levels of anaesthesia. We proposed a new index, non-rhythmic-to-rhythmic ratio (NRR), to quantify this feature and investigated its potential to estimate depth of anaesthesia., Methods: Thirty-one female patients were enrolled in this prospective study. The oscillatory pattern transition of RRI was visualised by the time-varying power spectrum and quantified by NRR. The prediction of anaesthetic events, including skin incision, first reaction of motor movement during emergence period, loss of consciousness (LOC) and return of consciousness (ROC) by NRR were evaluated by serial prediction probability (PK ) analysis; the ability to predict the decrease of effect-site sevoflurane concentration was also evaluated. The results were compared with Bispectral Index (BIS)., Results: NRR well-predicted first reaction (PK  > 0.90) 30 s ahead, earlier than BIS and significantly better than HRV indices. NRR well-correlated with sevoflurane concentration, although its correlation was inferior to BIS, while HRV indices had no such correlation. BIS indicated LOC and ROC best., Conclusions: Our findings suggest that NRR provides complementary information to BIS regarding the differential effects of anaesthetics on the brain, especially the subcortical motor activity., (© 2014 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Computerized tomography is a standard method for obtaining internal structure of objects from their projection images. While CT reconstruction requires the knowledge of the imaging directions, there are some situations in which the imaging directions are unknown, for example, when imaging a moving object. It is therefore desirable to design a reconstruction method from projection images taken at unknown directions. Another difficulty arises from the fact that the projections are often contaminated by noise, practically limiting all current methods, including the recently proposed diffusion map approach. In this paper, we introduce two denoising steps that allow reconstructions at much lower signal-to-noise ratios (SNRs) when combined with the diffusion map framework. In the first denoising step we use principal component analysis (PCA) together with classical Wiener filtering to derive an asymptotically optimal linear filter. In the second step, we denoise the graph of similarities between the filtered projections using a network analysis measure such as the Jaccard index. Using this combination of PCA, Wiener filtering, graph denoising, and diffusion maps, we are able to reconstruct the two-dimensional (2-D) Shepp-Logan phantom from simulative noisy projections at SNRs well below their currently reported threshold values. We also report the results of a numerical experiment corresponding to an abdominal CT. Although the focus of this paper is the 2-D CT reconstruction problem, we believe that the combination of PCA, Wiener filtering, graph denoising, and diffusion maps is potentially useful in other signal processing and image analysis applications.

We introduce vector diffusion maps (VDM), a new mathematical framework for organizing and analyzing massive high-dimensional data sets, images, and shapes. VDM is a mathematical and algorithmic generalization of diffusion maps and other nonlinear dimensionality reduction methods, such as LLE, ISOMAP, and Laplacian eigenmaps. While existing methods are either directly or indirectly related to the heat kernel for functions over the data, VDM is based on the heat kernel for vector fields. VDM provides tools for organizing complex data sets, embedding them in a low-dimensional space, and interpolating and regressing vector fields over the data. In particular, it equips the data with a metric, which we refer to as the vector diffusion distance . In the manifold learning setup, where the data set is distributed on a low-dimensional manifold ℳ d embedded in ℝ p , we prove the relation between VDM and the connection Laplacian operator for vector fields over the manifold.

The mechanisms regarding hepatic steatosis related to hepatic insulin resistance have been well documented. However, the agents for treatment of hepatic steatosis and insulin resistance remain poorly developed. Peroxisome proliferator-activated receptors (PPARs) are transcription factors that are responsible for the regulation of glucose and/or lipid metabolism. There are 3 distinct isoforms of PPARs family: PPARα, PPARγ, and PPARδ. Both PPARα and PPARγ agonists are widely used in clinic for the treatment of hyperlipidemia and hyperglycemia. However, the therapeutic efficacy of PPARδ agonists for diabetic disorders remains obscure. In the present study, we used L-165041 as PPARδ agonist to treat the high fat diet (HFD) fed mice. Administration of L-165041 improved the hepatic steatosis and increased the insulin sensitivity in HFD-mice. In addition to the histological identification of hepatic steatosis, the improvement of insulin sensitivity was characterized by the enhanced insulin signals and the increase of hepatic glycogen content. This is the first report showing that pharmacological activation of PPARδ improves insulin resistance in diet-induced diabetic mice. Thus, we suggest that pharmacological activation of PPARδ may be a new strategy for the treatment of diabetic patients with hepatic steatosis., (Georg Thieme Verlag KG Stuttgart · NewYork.)

The imidazoline I-1 receptor (I-1 R) agonists are widely used to lower blood pressure, but their effects on hyperlipidemia are still obscure. The present study is aimed to evaluate the possible mechanism(s) of I-1 R in the regulation of lipid homeostasis. Farnesoid X receptor (FXR) plays an important role in blood lipid homeostasis; however, the role of FXR in rilmenidine-induced blood lipid lowering action is still unknown. Thus, we administered rilmenidine, a selective agonist of I-1 R, into high fat diet-fed (HFD) mice showing hypertriglyceridemia and hypercholesterolemia. Rilmenidine significantly ameliorated hyperlipidemia in HFD mice after 7 days of administration. Pretreatment with efaroxan, at a dose sufficient to inhibit I-1 R activation, blocked the effects of rilmenidine. Also, in cultured HepG2 cells, rilmenidine dose-dependently induced the expression of farnesoid X receptor (FXR). The rilmenidine-induced FXR expression and FXR-related genes were blocked by efaroxan. However, rilmenidine treatment did not affect the expression of enzymes related to β-oxidation. In conclusion, activation of I-1 R may activate FXR to lower plasma lipids, suggesting I-1 R as a new target for the treatment of hyperlipidemia., (© Georg Thieme Verlag KG Stuttgart · New York.)

Racecadotril is an enkephalinase inhibitor used to treat abdominal discomfort in the clinic. The blood-glucose lowering action of racecadotril has been observed in rats; however, the mechanisms remain obscure. 8-week-old Wistar rats were intravenously injected with racecadotril and the levels of insulin in the brain were measured. Additionally, brain homogenates were co-incubated with racecadotril or thiorphan to evaluate insulin degrading enzyme (IDE) activity. Otherwise, rats were pretreated by intracerebroventricular (i. c. v.) injection of insulin antibody or glibenclamide at a dose sufficient to inhibit K (ATP) channels prior to injection of racecadotril. Moreover, rats were vagotomized to evaluate the role of the cholinergic nerve. Racecadotril significantly decreased the plasma glucose in rats; this action of racecadotril was abolished by i. c. v. pretreatment with insulin antibody or glibenclamide. Also, i. c. v. injection of thiorphan, the active form of racecadotril, lowered blood glucose, but this effect disappeared in the presence of the insulin antibody. In rat brain homogenates, racecadotril and thiorphan inhibited IDE activity and increased the cerebral insulin level. The blood-glucose lowering action of racecadotril or thiorphan was diminished in vagotomized rats. Our results suggest that racecadotril lowers blood glucose mainly through inhibition of IDE activity and increases endogenous insulin in the brain. Subsequently, the increased insulin might activate insulin receptor, which opens the K (ATP) channel and induces peripheral insulin release through the vagal nerve. Thus, we provide the new finding that racecadotril has the ability to inhibit IDE in rat brain., (© Georg Thieme Verlag KG Stuttgart · New York.)

Retinol binding protein 4 (RBP4) is an adipokine secreted by adipose tissue and liver and contributes to insulin resistance (IR) in animals. Although several human studies indicated that RBP4 is positively correlated with blood pressure and is elevated in untreated hypertensive subjects, the role of RBP4 in IR of hypertensive animals still remains obscure. In this study, spontaneously hypertensive rats (SHR) were used to investigate the relationship between RBP4 levels and IR. We found that at 7 weeks old, SHR had significantly increased plasma RBP4 levels and RBP4 expression in liver and epididymal adipose tissue accompanied by worsening of IR as compared with Wistar-Kyoto (WKY) control rats. Administration of fenretinide in SHR to increase urinary RBP4 excretion significantly decreased plasma RBP4 levels and improved IR. Moreover, treatment with valsartan markedly reduced blood pressure, circulating RBP4 and adiponectin levels, and IR in SHR. Valsartan also reversed the increase of hepatic gluconeogenic enzyme phosphoenolpyruvate carboxykinase (PEPCK) and the decrease of type 4 glucose transporter (GLUT4) in adipose tissue. In conclusion, these results suggest that RBP4 contributes, at least partly, to the pathogenesis of IR in SHR. Furthermore, the decrease of blood pressure caused by valsartan not only decreased RBP4 levels, but also improved IR in SHR., (© Georg Thieme Verlag KG Stuttgart · New York.)

Metformin is widely used in clinic for handling the diabetic disorders. However, action mechanisms of metformin remain obscure. It has recently been indicated that guanidinium derivatives are ligands to activate type-2 imidazoline receptors (I-2 receptors) that can improve diabetes through increment in skeletal muscle glucose uptake. Also, activation of I-2 receptors can increase the release of ß-endorphin in diabetic animals. Because metformin is a guanidinium derivative, we were interested in the effect of metformin on I-2 receptors. In the present study, the marked blood glucose-lowering action of metformin in streptozotocin-induced type-1 like diabetes rats was blocked by specific I-2 receptor antagonist, BU224, in a dose-dependent manner. Also, the increase of ß-endorphin release by metformin was blocked by BU224 in same manner. A specific competition between metformin and BU224 was observed in isolated adrenal medulla. Otherwise, amiloride at the dose sufficient to block I-2A receptor abolished the metformin-induced ß-endorphin release, but only the blood glucose-lowering action of metformin was markedly reduced. In addition, the blood glucose-lowering action of metformin in bilateral adrenalectomized rats was diminished by amiloride at higher doses. These results suggest that metformin might activate imidazoline I-2 receptors while I-2A receptors link the increase of ß-endorphin release and I-2B receptors couple to the other actions for lowering of blood glucose in type-1 like diabetic rats., (© Georg Thieme Verlag KG Stuttgart · New York.)

The aim of this study was to generate a transgenic mouse that ubiquitously expressed enhanced green fluorescent protein (EGFP) under the control of the murine phosphoglycerate kinase 1 promoter by allotransplantation of transgenic mouse ovaries. The EGFP transgenic mice expressed green fluorescence in many organs, and the fluorescence was detected as early as the embryonic stage. Ovaries from the EGFP transgenic mice were allotransplanted into recipients and these mice were mated with normal male mice. Histological sections of EGFP-allotransplanted ovaries from the recipient mice showed the well development and formation at follicles and corpora lutea. The green fluorescence was clearly detectable at the allotransplanted section of the ovaries, which had fused with the normal ovary. The average size of the first litter from these mice was 6.8 ± 1.2 pups per recipient, and 17.8% of the pups expressed EGFP. These results demonstrated that allotransplantation of transgenic ovaries can restore a normal reproductive lifespan and can be used to generate a ubiquitously expressing EGFP animal model., (© 2009 Blackwell Verlag GmbH.)

Inflammation is involved in the development of insulin resistance and diabetes. However, the effectiveness of anti-inflammatory drugs in diabetic therapy remains obscure. In the present study, the possible mechanisms of indomethacin, one of the nonsteroidal anti-inflammatory drugs, in the improvement of insulin resistance were investigated. Indomethacin treatment significantly decreased cotton pellet implantation induced white blood cell count elevation and immune cells infiltration in epididymal white adipose tissue. Also, cotton pellet implantation induced impaired glucose utilization and insulin resistance were improved by indomethacin. The decrement in phosphoinsulin receptor and phospho-Akt levels induced by cotton pellet implantation was improved by indomethacin as well. Moreover, indomethacin decreased cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expression in epididymal white adipose tissue with a marked reduction of prostaglandin 2 (PGE2) and nitrite/nitrate (NOx) levels in cotton pellet-implanted mice. Furthermore, pretreatment of peroxisome proliferator-activated receptor γ (PPARγ) antagonist, GW9662 not only reversed indomethacin-modified COX-2 and iNOS levels but also reversed indomethacin-improved insulin sensitivity determined by homeostasis model assessment-insulin resistance (HOMA-IR). Taken together, indomethacin might elevate the expression of PPARγ to decrease serum NOx and PGE2 to result in the improvement of insulin resistance., (© Georg Thieme Verlag KG Stuttgart · New York.)

Racecadotril is known as an inhibitor of enkephalinase. Increase of plasma insulin by racecadotril has been observed in rats while the mechanism of the action remains obscure. In the present study, intravenous injection of male Wistar rats with racecadotril significantly decreased blood glucose levels. However, this effect of racecadotril was not modified by naloxone at the dose sufficient to block opioid receptors. Thus, the blood glucose-lowering action of racecadotril might be through an endogenous opioid independent mechanism. Otherwise, we found that C-peptide content was also raised by racecadotril in parallel with the increase of insulin in Wistar rats. Thus, the blood glucose-lowering action of racecadotril was related to insulin secretion, but not through the inhibition of plasma insulin degradation. In addition, racecadotril showed no direct effect on insulin secretion in isolated islets or cultured HIT-T15 beta cells. The increase of plasma insulin and blood glucose-lowering action induced by racecadotril were reduced by pretreatment with atropine and enhanced by physotigmine. Direct inhibition of cholinesterase was not observed in brain homogenates treated with racecadotril. Moreover, actions of racecadotril were significantly reduced in rats receiving hemicholinium-3 at a sufficient dose to decrease endogenous acetylcholine. Activation of cholinergic tone is possibly involved in the blood glucose-lowering effect of racecadotril. Our results suggested that racecadotril increased insulin secretion to lower blood glucose mainly via regulation of parasympathetic tone in Wistar rats., (Georg Thieme Verlag KG Stuttgart New York.)

Glucosamine has been widely used to treat osteoporosis in clinic and it shows an effect on hexosamine biosynthetic pathway in glucose-induced insulin resistance. However, glucosamine and chronic hyperglycemia is not correlative. Thus, we used C (2)C (12) cell line to carry out the uptake assay of 2-[14C]-deoxy-d-glucose and [3H]-glucosamine. Glucosamine inhibited the in vitro glucose uptake in a concentration-dependent manner. The glucose transporter GLUT4 prepared for [3H]-glucosamine uptake showed a concentration-dependent competition between glucose and glucosamine uptake. The effects of glucosamine on glucose tolerance and homeostasis model assessment (HOMA) were also determined in normal Wistar and fructose-fed rats. Both plasma glucose levels and/or HOMA index were not changed in normal rats treated with glucosamine as compared with the saline-treated control. However, we found that glucosamine exhibited an effect on the expression of farnesoid X receptor in liver to exacerbate the values of HOMA and accelerate the development of insulin resistance in fructose-fed rats. Thus, glucosamine should be applied with caution in type-2 diabetic patients.

Aim: Transketolase-like enzyme 1 (TKTL1) is a glycolytic enzyme that has been found to be upregulated in several tumours, and it is associated with tumour progression. Nephroblastoma is the commonest paediatric renal malignancy and has a good prognosis except for those with anaplasia. To the best of the authors' knowledge, the expression of TKTL1 in nephroblastomas has not been studied before and the aim of this study was to compare the immunoexpression of TKTL1 in anaplastic and non-anaplastic nephroblastomas., Methods: Twenty-eight patients who had nephrectomies for nephroblastomas were studied. Archival formalin-fixed paraffin-wax-embedded tissue sections were stained with monoclonal TKTL1 antibody., Results: Six of the 15 anaplastic nephroblastomas showed staining in 80-100% of the tumour (p = 0.36). None of the 13 non-anaplastic nephroblastomas showed TKTL1 staining in >80% of the tumour., Conclusion: TKTL1 expression is associated with the presence of anaplasia and may be a mechanism via which anaplastic tumour cells thrive under different conditions. Glycolytic inhibitors may play a role in anaplastic nephroblastomas.

Aims: To examine algino-oligosaccharide production by alginase from newly isolated Flavobacterium sp. LXA and its elicitor and antibacterial activity., Methods and Results: Algino-oligosaccharide production from alginate was carried out using alginase obtained from a newly isolated Flavobacterium sp. LXA. When alginase was partially purified by dual ammonium sulfate precipitation and used for alginate degradation, the viscosity loss correlated well with the release of reducing terminals. The optimal temperature and pH for alginate degradation was 40 degrees C and pH 7.0, respectively. When alginate was added at an initial concentration of more than 0.8%, the maximal degradation rate of alginate was obtained. Under these optimal reaction conditions and with partially purified alginase, the average degrees of polymerization (DP) of alginate-degraded products was about 6.0, which favoured algino-oligosaccharide production. The algino-oligosaccharides showed an elicitor activity stimulating the accumulation of phytoalexin and inducing phenylalanine ammonia lyase in soybean cotyledon, and antimicrobial activity on Pseudomonas aeruginosa., Conclusions: Algino-oligosaccharide could be degraded from alginate by the partially purified alginase and its maximal bioactivity occurred on the oligosaccharide with average DP 6.8., Significance and Impact of the Study: Algino-oligosaccharide was first reported to have elicitor and antibacterial activity and have potential as a biological agent for protection against plant or human disease.