[Value of surgery combined chemotherapy and radiation therapy in locally advanced neuroendocrine carcinoma of the cervix: a single-center retrospective cohort study].

Objective: To evaluate the surgery combined chemotherapy and radiation in locally advanced neuroendocrine carcinoma of the cervix (NECC) . Methods: This is a single-center retrospective cohort study. Locally advanced NECC patients admitted to Peking Union Medical College Hospital, Chinese Acadmy of Medical Sciences from January 2011 to April 2022 were enrolled. They were divided into concurrent chemoradiotherapy group, and surgery combined with chemotherapy and radiation group. The Kaplan-Meier method was used to analyze the progression free survival (PFS), overall survival (OS), recurrence rate, and mortality rate. Results: (1) Forty-six cases were included, 22 in concurrent chemoradiotherapy group, 24 in surgery combined chemotherapy and radiation group. With 16 patients (35%, 16/46) received neoadjuvant chemotherapy (NACT), the NACT effective rate was 15/16. (2) The median follow-up time was 27.5 months (range: 10-106 months), with 26 (57%, 26/46) experienced recurrences. There were 4 (9%, 4/46) pelvic recurrences and 25 (54%, 25/46) distant recurrences, and 3 (7%, 3/46) both pelvic and distant recurrences. Compared with concurrent chemoradiotherapy group, surgery combined chemotherapy and radiation group had lower pelvic recurrence rate [14% (3/22) vs 4% (1/24); χ2=1.296, P=0.255] but without statistic difference. Both groups had similar distant recurrence rate [55% (12/22) vs 54% (13/24); χ2=0.001, P=0.979] and overall recurrence rate [59% (13/22) vs 54% (13/24); χ2=0.113, P=0.736]. (3) During the follow-up period, 22 cases (48%, 22/46) died, with 11 cases (50%, 11/22) in concurrent chemoradiotherapy group and 11 cases (46%, 11/24) in surgery combined chemotherapy and radiation group, without significant difference (χ2=0.080, P=0.777). The postoperative 3-year and 5-year OS rates were 62.3% and 36.9%. Compared with concurrent chemoradiotherapy group, the patients in surgery combined chemotherapy and radiation group showed an extended trend in PFS (17.0 vs 32.0 months) and OS (37.0 vs 50.0 months) but without statistic differences (P=0.287, P=0.125). Both groups had similar 3-year OS rate (54.2% vs 69.9%; P=0.138) and 5-year OS rate (36.1% vs 38.8%; P=0.217). Conclusions: Our study supports the multi-modality treatment strategy (including surgery, chemotherapy and radiation) as an important component in the treatment of locally advanced NECC. The combination of surgery, chemotherapy and radiation seems to have advantages in the treatment of locally advanced NECC, but needs to be confirmed by further multicenter studies.

[Value of postoperative radiotherapy and analysis of prognostic factors in early-stage neuroendocrine carcinoma of cervix].

Objective: To evaluate the effect of postoperative radiotherapy and high-risk pathological factors on the prognosis of early-stage neuroendocrine carcinoma of cervix (NECC). Methods: A single-center retrospective cohort study of early-stage NECC in Peking Union Medical College Hospital from January 2011 to April 2022 were enrolled. The patients were treated with radical hysterectomy±adjuvant treatment. They were divided into postoperative non-radiation group and postoperative radiation group. The possible postoperative recurrence risk factors identified by univariate analysis were assessed using multivariate logistic regression. The Kaplan-Meier method was used to analyze the progression free survival (PFS), overall survival (OS), recurrence rate, and mortality rate. Results: (1) Sixty-two cases were included in the study, including 33 cases in postoperative non-radiation group and 29 cases in postoperative radiation group. (2) The median follow-up time was 37 months (ranged 12-116 months), with 23 cases (37%) experienced recurrences. There were 7 cases (11%) pelvic recurrences and 20 cases (32%) distant recurrences, in which including 4 cases (6%) both pelvic and distant recurrences. Compared with postoperative non-radiation group, the postoperative radiation group had a lower pelvic recurrence rate (18% vs 3%; P=0.074) but without statistic difference, a slightly elevated distant recurrence rate (24% vs 41%; P=0.150) and overall recurrence rate (33% vs 41%; P=0.513) without statistically significances. Univariate analysis showed that lymph-vascular space invasion and the depth of cervical stromal invasion≥1/2 were risk factors for postoperative recurrence (all P<0.05). Multivariate analysis showed lymph-vascular space invasion was an independent predictor for postoperative recurrence (OR=23.03, 95%CI: 3.55-149.39, P=0.001). (3) During the follow-up period, 18 cases (29%, 18/62) died with tumor, with 10 cases (30%, 10/33) in postoperative non-radiation group and 8 cases (28%, 8/29) in postoperative radiation group, without significant difference (P=0.814). The postoperative 3-year and 5-year survival rate was 79.2%, 60.8%. The depth of cervical stromal invasion≥1/2 was more common in postoperative radiation group (27% vs 64%; P=0.011), and postoperative radiation in such patients showed an extended trend in PFS (32.3 vs 53.9 months) and OS (39.4 vs 73.4 months) but without statistic differences (P=0.704, P=0.371). Compared with postoperative non-radiation group, the postoperative radiation did not improve PFS (54.5 vs 37.3 months; P=0.860) and OS (56.2 vs 62.4 months; P=0.550) in patients with lymph-vascular space invasion. Conclusions: Postoperative radiation in early-stage NECC patients has a trend to reduce pelvic recurrence but not appear to decrease distant recurrence and overall recurrence, and has not improved mortality. For patients with the depth of cervical stromal invasion≥1/2, postoperative radiation has a trend of prolonging OS and PFS but without statistic difference. Lymph-vascular space invasion is an independent predictor for postoperative recurrence, but postoperative radiation in such patients does not seem to have any survival benefits.

Detection of self-biting behavior of mink by loop-mediated isothermal amplification (LAMP) and sequence-characterized amplified regions (SCAR).

Self-biting disease occurs in most farmed fur animals in the world. The mechanism and rapid detection method of this disease has not been reported. We applied bulked sergeant analysis (BSA) in combination with RAPD method to analyze a molecular genetic marker linked with self-biting trait in mink group. The molecular marker was converted into SCAR and loop-mediated isothermal amplification (LAMP) marker for rapid detection of this disease. A single RAPD marker A10 amplified a specific band of 1000bp in self-biting minks. The sequences of the bands exhibited 73% similarity to the Canis Brucella. SCAR and LAMP marker were designed for the specific fragment of RAPD marker A10 and validated in 30 self-biting minks and 30 healthy minks. c2 test showed difference (p0.05) with SCAR and significant difference (p0.01) with LAMP in the detection rate between the two groups, but LAMP method was more accurate than SCAR method. This indicated that LAMP can be used as a positive marker to detect self-biting disease in minks.

[Prospective cohort study on the outcomes of sacrospinous ligament fixation using conventional instruments in treating stage â ¢-â £ pelvic organ prolapse].

Objective: To evaluate the medium and long term safety and efficacy of sacrospinous ligament fixation (SSLF) performed with conventional instruments in treating stage Ⅲ-Ⅳ pelvic organ prolapse (POP). Methods: A prospective cohort analysis was conducted in the Peking Union Medical College Hospital, between May 2007 and June 2015, enrolling 55 women with stage Ⅲ-Ⅳ POP who intended to receive SSLF. Primary end points were objective success rates using pelvic organ prolapse quantitation system (POP-Q) and subjective satisfaction rates with questionnaires after surgery according to vaginal examination and related questionnaires for all patients who received SSLF eventually. Exploratory outcomes included perioperative parameters and complications. Results: Of these 55 POP patients enrolled, 52 (95%, 52/55) received SSLF using conventional surgical instruments, the other 3 cases converted to ischial spinous fascia fixation due to difficulty exposing. Medium blood loss during operation was 100 ml (20-300 ml) and operative time 60 minutes (20-165 minutes). Pelvic hematoma with diameters of 5 cm and 7 cm were observed in two patients, both recovered fully with conservative methods. All patients were able to micturate spontaneously after catheter withdrawal. One patient reported right thigh pain after operation which remained till 3-month follow-up and relieved after physiotherapy. The objective success rate was 100% (52/52) at 3 months. With a medium follow-up time of 23.7 months, the objective success rate was 98% (51/52), the recurrence rate was 2% (1/52) and the satisfactory rate was 94% (49/52). De novo urinary incontinence occurred in 6% (3/52) of patients. Conclusion: Most POP could be corrected with SSLF using conventional instruments which is a feasible, economic and effective procedure for Asian patients with medium compartment prolapse.

Bioinformatic analysis based on the complete coding region of the MSTN gene within and among different species.

Myostatin, encoded by the MSTN gene (previously GDF8), is a member of the transforming growth factor-ß superfamily, which normally acts to limit skeletal muscle mass by regulating the number and growth of muscle fibers. In this study, a total of 84 myostatin gene sequences with known complete coding regions (CDS) and corresponding amino acid sequences were analyzed from 17 species, and differentiation within and among species was studied using comparative genomics and bioinformatics. Characteristics of the nucleotide and amino acid sequences were also predicted. The results indicated that a total of 569 polymorphic sites, including 53 singleton variable sites and 516 parsimony informative sites, which could be sorted into 44 haplotypes, were detected from 17 species. Observed genetic diversity was higher among species than within species, and Vulpes lagopus was more polymorphic than other species. There was clear differentiation of the myostatin gene among species and the reconstructed phylogenetic tree was consistent with the NCBI taxonomy. The myostatin gene was 375-aa long in most species, except for Mus musculus (376 aa) and Danio rerio (373 aa). The amino acid sequences of myostatin were deemed hydrophilic, and had theoretical pI values of <7.0, mostly due to the acidic polypeptide. The instability index of the myostatin protein was 40.48-51.63, indicating that the polypeptide is not stable. The G+C content of the CDS nucleotide sequence in different species was 40.60-51.69%. The predicted promoter region of the Ovis aries myostatin gene was 150-220 bp upstream of the start codon.

[Functional mapping of the insular and opercular cortex: A study using SEEG electrical stimulation in epileptic patients].

OBJECTIVE: Insular and opercular cortex is involved in complicated physiological function.Insular seizures involve extensive epileptic network, which results in the complex and diverse semiology.Electrical cortical stimulation(ECS) can explore the functional mapping and symptomatogenic zone. METHODS: The clinical presurgical evaluation and ECS data of 20 patients whose electrode contacts were located in the insular and opercular were analyzed retrospectively.CT scan/3D MRI data fusion was performed in order to accurately identify and locate each contact and check the electrode trajectory by the MRI images performed after the electrodes were removed.ECS was applied between two contiguous contacts.Stimulation usually lasted for 5 s at 50 Hz(pulse width=0.3 ms). Depending on the area of stimulated cortex, the stimulation intensities ranged from 0.2 to 3.0 mA.The classification of the insular were anterior short gyrus, middle short gyrus, precentral gyrus, postcentral gyrus, posterior long gyrus and insular pole.The classification of the opercular were orbital, frontal, precentral, central, parietal and temporal opercular. RESULTS: One hundred and six contacts were located in the insular and 51 responses were evoked (48.11%). Four hundred eighteen contacts were located in the insular and 132 responses were evoked (31.58%). We classified the principal responses as somatosensory, pain, auditory, oropharyngeal, speech disturbances and neurovegetative response.Somatosensory responses were mainly evoked in parietal opercular and postcentral gyrus, while pain response distributed sporadically.Auditory were only evoked in temporal opercular(transverse temporal gyri) and posterior long gyrus.Oropharyngeal symptoms were only evoked in central opercular.Speech disturbances were located in precentral and central opercular and neurovegetative responses were mainly evoked in insular pole and middle short gyrus. CONCLUSIONS: These findings may indicate a functional specificity for the insular gyrus and opercular, which contribute to the understanding of anatomo-functional organization and the role in insular and opercular epileptic network.Moreover, it could optimize the implantation strategy for exploring these structures.

[Analysis of risk factors and construction of nomogram model for local lymph node metastasis in salivary gland mucoepidermoid carcinoma].

Objective: To analyze the risk factors affecting regional lymph node metastasis in salivary gland mucoepidermoid carcinoma (MEC) and to establish a nomogram model for individually predicting lymph node metastasis in salivary gland MEC. Methods: The clinical data of 2 152 patients with salivary gland MEC from 1975 to 2020 were collected from the Surveillance, Epidemiology, and End Results (SEER) database of the National Cancer Institute. The collected data were divided into training cohort (1 506 cases) and validation cohort (646 cases) according to the ratio of 7∶3. Single-factor regression and multi-factor logistic regression were used to screen factors related to local lymph node metastasis in salivary gland MEC, with constructing of a nomogram. Calibration curve, receiver operating characteristic (ROC) curve, area under the ROC curve (AUC) and decision curve analysis were used to evaluate model performance in the validation cohort and the total cohort. Statistical tests were performed using SPSS (26.0) and R (4.3.0) software. Results: Multivariate logistic regression results showed that M stage [OR(95%CI):12.360(3.295-46.365), P=0.014], pathological grade Ⅱ、Ⅲ、Ⅳ[OR(95%CI): 1.956(1.329-2.879), 9.654(6.309-14.772), 9.298(6.072-14.238), P<0.001], T staging T2, T3, T4[OR(95%CI): 1.706(0.932-3.124), 3.021(1.790-5.096), 3.311(1.925-5.695), P<0.001], and gender [OR(95%CI):0.759(0.593-0.972), P=0.029] were independent factors affecting local lymph node metastasis in salivary gland MEC. Through verification in the validation cohort and the total cohort, the AUC values were greater than 0.8, and the calibration curve was close to the perfect reference line, proving that the constructed nomogram model had good specificity and sensitivity for predicting local lymph node metastasis in salivary gland MEC. Conclusion: M stage, pathological grade, T stage, and gender are risk factors for predicting regional lymph node metastasis and the established-nomogram has good predictive performance for local lymph node metastasis in salivary gland MEC.

[Screening and validation of therapeutic targets for chronic sinusitis with nasal polyps based on proteomics].

Objective: To identify potential therapeutic targets of chronic sinusitis with nasal polyps (CRSwNP) through proteomics screening of and verify its effectiveness experimentally. Methods: The nasal tissue samples were collected from patients undergoing surgical treatment in the Department of Otorhinolaryngology, Head and Neck Surgery in Yuhuangding Hospital of Yantai from June 2010 to December 2021, including 69 patients with CRSwNP and 39 patients in the control group. Tissue samples were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) in data-independent acquisition (DIA) mode to find differentially expressed proteins. Bioinformatics tools were employed to analyze the functions of differentially expressed proteins. The expression of hematopoietic cell kinase (HCK) in nasal tissues of patients with CRSwNP was further confirmed by qPCR and western blot. The mouse model of CRSwNP was established and treated with HCK inhibitor. The levels of inflammatory factors IgE, IL-4 and IL-5 in serum of CRSwNP mice, both treated and untreated with HCK inhibitors, were detected by enzyme-linked immunosorbent assay (ELISA) across different experimental groups. The experimental data were analyzed by Graphpad Prism 9 software. Results: DIA analysis identified 1 850 differential proteins, including 760 up-regulated proteins and 1 090 down-regulated proteins. Weighted correlation network analysis (WGCNA) correlation analysis of phenotypic data such as cell count and CT score with the results of genomics indemnified 575 proteins of MEBrown module which intersected with 35 kinases further screened from 1 850 differential proteins, yielding eight protein kinases: HCK, SYK, PDK2, FGR, PRKCB, ROR1, CAMK1 and GRK6. qPCR showed that the expression of HCK in CRSwNP was significantly higher than that in the control group (P<0.05). Further experiments in mice confirmed that the secretion of IgE, IL-4 and IL-5 in the serum of CRSwNP group was significantly higher than the control group (all P<0.05), indicating successful model establishment. The intervention of HCK significantly decreased the secretion of IgE, IL-4 and IL-5 in serum of mice (all P<0.05). Conclusion: The HCK inhibitor can reduce the inflammatory index of mice with CRSwNP, and HCK is a potential therapeutic target of CRSwNP.

[Efficacy of allogeneic hematopoietic stem cell transplantation based on a total body irradiation conditioning treatment regimen for adult acute lymphocytic leukemia].

Objective: To analyze the efficacy of allo-HSCT with total body irradiation (TBI) and chemotherapy alone in the treatment of adult ALL and to explore the factors affecting prognosis. Methods: The clinical data of 95 adult patients with ALL who underwent allo-HSCT from January 2015 to August 2022 were included. According to the conditioning regimen, the patients were divided into two groups: the TBI plus cyclophosphamide (TBI/Cy) group (n=53) and the busulfan plus cyclophosphamide (Bu/Cy) group (n=42). Hematopoietic reconstitution after transplantation, GVHD, transplantation-related complications, relapse rate (RR), non-relapse mortality (NRM), OS, and LFS were compared, and the factors related to prognosis were analyzed. Results: The median time of neutrophil engraftment was 14 (10-25) days in the TBI/Cy group and 14 (10-24) days in the Bu/Cy group (P=0.106). The median time of megakaryocyte engraftment was 17 (10-42) days in the TBI/Cy group and 19 (11-42) days in the Bu/Cy group (P=0.488). The incidence of grade Ⅱ-Ⅳ acute GVHD (aGVHD) in the TBI/Cy and Bu/Cy groups was 41.5% and 35.7%, respectively (P=0.565). The incidence of grade Ⅲ-Ⅳ aGVHD in these two groups was 24.5% and 4.8%, respectively (P=0.009). The incidence of severe chronic GVHD in the two groups was 16.7% and 13.5%, respectively (P=0.689). The incidence of cytomegalovirus infection, Epstein-Barr virus infection, severe infection, and hemorrhagic cystitis in the two groups was 41.5% and 35.7% (P=0.565), 34.0% and 35.7% (P=0.859), 43.4% and 33.3% (P=0.318), and 20.8% and 50.0% (P=0.003), respectively. The median follow-up time was 37.1 months and 53.3 months in the TBI/Cy and Bu/Cy groups, respectively. The 2-year cumulative RR was 17.0% in the TBI/Cy group and 42.9% in the Bu/Cy group (P=0.017). The 2-year cumulative NRM was 24.5% and 7.1%, respectively (P=0.120). The 2-year LFS was 58.5% and 50.0%, respectively (P=0.466). The 2-year OS rate was 69.8% and 64.3%, respectively (P=0.697). In the multivariate analysis, the conditioning regimen containing TBI was a protective factor for relapse after transplantation (HR=0.304, 95% CI 0.135-0.688, P=0.004), whereas the effect on NRM was not significant (HR=1.393, 95% CI 0.355-5.462, P=0.634). Infection was an independent risk factor for OS after allo-HSCT in adult patients with ALL. Conclusion: allo-HSCT based on TBI conditioning regimen had lower relapse rate and lower incidence of hemorrhagic cystitis for adult ALL, compared with chemotherapy regimen. While the incidence o grade Ⅲ/Ⅳ aGVHD was hgher in TBI conditioning regimen than that in chemotherapy regimen.

[Incidence and prognosis of olfactory and gustatory dysfunctions related to infection of SARS-CoV-2 Omicron strain: a national multi-center survey of 35 566 population].

Objective: This cross-sectional investigation aimed to determine the incidence, clinical characteristics, prognosis, and related risk factors of olfactory and gustatory dysfunctions related to infection with the SARS-CoV-2 Omicron strain in mainland China. Methods: Data of patients with SARS-CoV-2 from December 28, 2022, to February 21, 2023, were collected through online and offline questionnaires from 45 tertiary hospitals and one center for disease control and prevention in mainland China. The questionnaire included demographic information, previous health history, smoking and alcohol drinking, SARS-CoV-2 vaccination, olfactory and gustatory function before and after infection, other symptoms after infection, as well as the duration and improvement of olfactory and gustatory dysfunction. The self-reported olfactory and gustatory functions of patients were evaluated using the Olfactory VAS scale and Gustatory VAS scale. Results: A total of 35 566 valid questionnaires were obtained, revealing a high incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain (67.75%). Females(χ2=367.013, P<0.001) and young people(χ2=120.210, P<0.001) were more likely to develop these dysfunctions. Gender(OR=1.564, 95%CI: 1.487-1.645), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), oral health status (OR=0.881, 95%CI: 0.839-0.926), smoking history (OR=1.152, 95%CI=1.080-1.229), and drinking history (OR=0.854, 95%CI: 0.785-0.928) were correlated with the occurrence of olfactory and taste dysfunctions related to SARS-CoV-2(above P<0.001). 44.62% (4 391/9 840) of the patients who had not recovered their sense of smell and taste also suffered from nasal congestion, runny nose, and 32.62% (3 210/9 840) suffered from dry mouth and sore throat. The improvement of olfactory and taste functions was correlated with the persistence of accompanying symptoms(χ2=10.873, P=0.001). The average score of olfactory and taste VAS scale was 8.41 and 8.51 respectively before SARS-CoV-2 infection, but decreased to3.69 and 4.29 respectively after SARS-CoV-2 infection, and recovered to 5.83and 6.55 respectively at the time of the survey. The median duration of olfactory and gustatory dysfunctions was 15 days and 12 days, respectively, with 0.5% (121/24 096) of patients experiencing these dysfunctions for more than 28 days. The overall self-reported improvement rate of smell and taste dysfunctions was 59.16% (14 256/24 096). Gender(OR=0.893, 95%CI: 0.839-0.951), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), history of head and facial trauma(OR=1.180, 95%CI: 1.036-1.344, P=0.013), nose (OR=1.104, 95%CI: 1.042-1.171, P=0.001) and oral (OR=1.162, 95%CI: 1.096-1.233) health status, smoking history(OR=0.765, 95%CI: 0.709-0.825), and the persistence of accompanying symptoms (OR=0.359, 95%CI: 0.332-0.388) were correlated with the recovery of olfactory and taste dysfunctions related to SARS-CoV-2 (above P<0.001 except for the indicated values). Conclusion: The incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain is high in mainland China, with females and young people more likely to develop these dysfunctions. Active and effective intervention measures may be required for cases that persist for a long time. The recovery of olfactory and taste functions is influenced by several factors, including gender, SARS-CoV-2 vaccination status, history of head and facial trauma, nasal and oral health status, smoking history, and persistence of accompanying symptoms.

[Correlation analysis of clock genes and MEN2 medullary thyroid carcinoma].

Objective: To investigate the correlation between CLOCK and BMAL1 genes and MEN2 medullary thyroid carcinoma (MTC). Methods: Thirteen cases with MEN2 MTC and thirteen cases with non-MEN2 MTC were selected who were treated in the Yantai Yuhuangding Hospital between January 2013 and September 2021. Clinical indicators such as blood calcitonin level, tumor diameter and metastatic lymph node of patients were collected. The expression differences of CLOCK and BMAL1 between MEN2 MTC and para-carcinoma tissue as well as between MEN2 MTC and non-MEN2 MTC were detected by immunohistochemistry and qPCR. The correlation between lymph node metastasis and CLOCK or BMAL1 expression was analyzed. Protein-protein interaction (PPI) network analysis combined with qPCR and correlation analysis was used to explore the expression regulation relationship between RET and circadian clock genes. The rhythm disorder of MEN2 cells was verified by lipopolysaccharide cell stimulation experiment after dexamethasone rhythm synchronization. Results: MEN2 MTC exhibited typical RET gene mutation. The mean blood calcitonin level, the tumor diameter and the number of metastatic lymph nodes of patients with MEN2 MTC were higher than those of patients with non-MEN2 MTC (t value was 2.76, 2.53, 2.26, all P<0.05). Immunohistochemical results showed that the expression levels of CLOCK and BMAL1 in MEN2 MTC were higher than those in non-MEN2 MTC, while negatively expressed in para-cancerous thyroid follicle. qPCR displayed that the expression of CLOCK gene in cancer tissues was higher than that in non-MEN2 MTC and para-cancerous tissues (t value was 2.68 and 2.86, all P<0.05); the expression of BMAL1 gene in MEN2 MTC was higher than that in non-MEN2 MTC and para-cancerous tissues (t value was 2.21 and 2.35, all P<0.05). Correlation analysis showed that the expression levels of CLOCK and BMAL1 genes were positively correlated with the number of lymph node metastases in patients with MEN2 MTC (r=0.65, P<0.001; r=0.52, P=0.005). PPI network analysis indicated that the expression of CLOCK gene was positively correlated with the abnormal expression of RET gene (r=0.96, P<0.001). With lipopolysaccharide to stimulate cultured cells in vitro after dexamethasone rhythm synchronization, the expressions of CLOCK and BMAL1 in MEN2 MTC cells (0.47±0.22 and 2.60±1.48) at 12 hours of synchronization were significantly lower than those in para-cancerous tissues (1.70±1.62 and 8.23±2.52), the difference was statistically significant(t=5.04, P=0.007; t=3.34, P=0.029). Conclusion: CLOCK and BMAL1 are correlated with the occurrence and development of MEN2 MTC, and may be potential targets for the development of new therapeutic strategies for MEN2 MTC.

[Application of enhanced recovery after surgery in laryngeal cancer surgery with multi-disciplinary team].

Objective: To explore the application value of enhanced recovery after surgery (ERAS) with the multidisciplinary team (MDT) model in laryngeal cancer surgery. Methods: Eighty patients with laryngeal cancer treated in Department of Otorhinolaryngology Head and Neck Surgery of Yantai Yuhuangding Hospital from May 2016 to June 2017 were selected, including 76 males and 4 females, aged 45 to 75 years old. By random number table method, they were divided into ERAS group (40 cases) and control group (40 cases). Visual analogue scale (VAS), general comfort questionnaire (GCQ) and self-rating Anxiety Scale (SAS) were used to evaluate the symptoms and signs and psychological state of the two groups before and after operation. Mann Whitney U test was used for non-normal distribution data, and chi square test, Fisher exact probability method and covariance analysis were used for classification data. Repeated measures analysis of variance was used for the comparison of each group at different time points. Results: Two cases in the ERAS group and six cases in the control group withdrew from the study for some reason. Finally, 38 cases in the ERAS group and 34 cases in the control group were enrolled in this study. The postoperative pain scores of the two groups were the highest at 6 h after operation, and then gradually decreased. At different time points after operation, the pain scores of ERAS group were lower than those of the control group. At 24 h after operation, the pain relief degree of ERAS group was significantly higher than that of the control group, with a statistically significant difference (P<0.05). Compared to control group, ERAS group had lower preoperative thirst score [(0.15±0.36) vs. (4.29±1.17), Z=-7.695, P<0.001] and hunger score [(0.38±0.49) vs. (3.44±1.13), Z=-7.426, P<0.001]. The total number of postoperative adverse reactions (8 vs.16), oral feeding time [(4.06±4.42) d vs. (9.06±2.42) d] and postoperative hospital stay [(5.91±0.97) d vs. (11.03±2.11)d] in ERAS group were lower than those in control group (statistics 5.461, -4.558, -7.347, P<0.05), but there was no significant difference in postoperative catheter indwelling time and neck drainage tube indwelling time between the two groups (P>0.05). Before discharge, the comfort of ERAS group was significantly higher than that of control group [(60.37±8.78) vs. (50.38±8.08), Z=-4.370, P<0.001]. Before discharge, the anxiety level of ERAS group decreased, while that of the control group increased significantly, which was higher than that of ERAS Group [(59.12±6.43) vs. (52.62±6.25), Z=-4.179, P<0.001]. Conclusion: The application of multidisciplinary ERAS in laryngeal cancer surgery can improve preoperative hunger and thirst, postoperative pain and mental state, shorten the length of hospital stay and reduce postoperative adverse reactions.

[Clinical genetic analysis and diagnosis of a family with hereditary hemorrhagic telangiectasia].

Objective: To explore the diagnostic significance of the combination of clinical and genetic detection of hereditary hemorrhagic telangiectasia (HHT) by analyzing the clinical and genetic diagnosis of a family with HHT. Methods: Medical history data of the probands and their family members were collected, and the sequence analyses of coding regions of ENG, ACVRL1, SMAD4 and GDF2 genes were performed by PCR-sequencing method, and a comprehensive diagnosis was made based on the clinical features and gene detection results. After the pathogenic gene variation was identified, 11 members of 3 generations of the family were tested for pathogenic gene mutation. Results: There was an ACVRL1 c.715_716delAG mutation in the proband and 9 other family members, which caused p.S239C. Based on the clinical and genetic findings, the 7 suspected were diagnosed and 2 asymptomatic patients were found to carry the mutation site. Conclusion: The combination of clinical features and gene detection can determine the etiology and classification of HHT, which is convenient for the early diagnosis and prevention of the disease.

[Perioperative airway management based on enhanced recovery after surgery for improvement of preoperative pulmonary function in patients with aspirin intolerance triad].

Objective: To explore the effect of perioperative airway management based on the concept of enhanced recovery after surgery (ERAS) on the improvement of preoperative pulmonary function in patients with aspirin intolerance triad (AIT). Methods: Thirty patients with AIT (including 13 males and 17 females, aged from 29 to 75 years old) for sinus surgery from January 2018 to December 2019 were selected, 172 patients (including 105 males and 67 females, aged from 17 to 83 years old) with chronic rhinosinusitis with nasal polyps (CRSwNP) without lower airway disease were selected by random number table at the same period, and their clinical data and preoperative pulmonary function were analyzed and compared retrospectively. FEV1%pred<80% after bronchodilation test was considered as high risk for surgery. Preoperative evaluation and standardized drug intervention were applied in patients with pulmonary function abnormalities at risk for surgery, and improvement of preoperative pulmonary function and tolerability to general anesthesia surgery in the two groups were evaluated. All the statistical analyses were conducted using SPSS 22.0. Results: The main pulmonary function indexes (FEV1%pred, FEV1/FVC%pred, FEF50%pred, FEF75%pred, MMEF%pred) in AIT group decreased significantly than those in CRSwNP group (t values were 10.882, 10.506, 9.141, 10.182, 9.099, respectively, all P<0.001). At admission 86.7% (26/30) patients in the AIT group and 11.6% (20/172) patients in CRSwNP group had high surgical risk for lung function, with significantly difference (χ2 = 81.788, P<0.05); after 3 days with individualized drug intervention, 57.7% (15/26) patients in AIT group reached the standard for surgery, which was significantly less than 90.0% (18/20) patients in CRSwNP group (χ²=4.335,P<0.05); and after 6 days with drug intervention, the patients who reached the standard for surgery in pulmonary function accounted for 92.3% (24/26) in the AIT group and 100% (20/20) in the CRSwNP group. FEV1%pred in the two groups before surgery were significantly improved compared with those at admission respectively ((90.00±6.32)% vs. (64.79±13.60)%,t value was 10.110 in AIT group; (91.65±11.86)% vs. (76.40±9.35)%, t value was 9.346 in CRSwNP group; all P<0.05), and also FEV1/FVC%pred, FEF50%pred, FEF75%pred and MMEF%pred were all significantly improved (all P<0.05). Surgery was completed successfully in the two groups of patients with lung function meeting the surgical standard, and no intraoperative or postoperative airway adverse events occurred. Conclusion: AIT patients have high airway risk for sinus surgery due to poor pulmonary function. Standardized airway management based on the concept of ERAS can improve the pulmonary function of patients, and decrease the incidence of perioperative airway adverse events.

[Clinical analysis of 61 cases of deep neck infection].

Objective: To explore the clinical experience in care for deep neck infection (DNI) and to analyze the factors influencing surgical treatment outcome. Methods: A retrospective analysis was conducted on 61 patients with DNI admitted to the Department of Otorhinolaryngology Head and Neck Surgery of Yantai Yuhuangding Hospital from March 2013 to April 2019, including 33 males and 28 females, aged from 6 months to 81 years with a median age of 49 years. Patients were divided into two groups, 31 cases with localized infection (neck abscess) in Group A and 30 cases with diffuse infection (neck necrotizing fasciitis) in Group B. Patients in two groups were compared for sex, age, hospital stay, diabetes, tracheostomy, drainage methods, mediastinal infection, and pathogenic bacteria. The influence of different drainage methods on hospital stay in Group A was analyzed. SPSS 25.0 software was used for statistical analysis. Results: Of the 61 patients, 45 patients underwent surgical incision and drainage (21 cases in Group A and 24 cases in Group B), 23 patients underwent ultrasound-guided fine needle aspiration (UG-FNA) and catheter drainage (10 cases in Group A and 13 cases in Group B), and 7 patients in Group B were treated with both drainage methods. Pathogens were cultured in 31 cases (50.82%). There were significant differences in hospital stay, drainage method and mediastinal infection (χ(2) values were 26.890, 8.687 and 6.035, respectively, P<0.05), but no significant difference was found in sex, age, diabetes, tracheotomy and pathogenic bacteria (χ(2) values were 0.157, 3.685, 2.434, 3.631 and 0.807, respectively, P>0.05) between the two groups. There was no significant difference in hospital stay between two drainage methods in patients in Group A (χ(2)=1.560, P>0.05). Conclusions: There were significant differences in hospital stay, drainage method and mediastinal infection between patients with localized infection and diffuse infection, as diffuse infection is often associated with serious complications. UG-FNA and catheter drainage is an optional method for the treatment of localized infection, with minimal invasion and no influence on hospital stay.

[Radiomics nomogram of MR: a prediction of cervical lymph node metastasis in laryngeal cancer].

Objective: To establish and validate a radiomics nomogram based on MR for predicting cervical lymph node metastasis in laryngeal cancer. Methods: One hundred and seventeen patients with laryngeal cancer who underwent MR examinations and received open surgery and neck dissection between January 2016 and December 2019 were included in this study. All patients were randomly divided into a training cohort (n=89) and test cohort (n=28) using computer-generated random numbers. Clinical characteristics and MR were collected. Radiological features were extracted from the MR images. Enhanced T1 and T2WI were selected for radiomics analysis, and the volume of interest was manually segmented from the Huiyihuiying radiomics cloud platform. The variance analysis (ANOVA) and the least absolute shrinkage and selection operator (LASSO) algorithm were used to reduce the dimensionality of the radiomics features in the training cohort. Then, a radiomic signature was established. The clinical risk factors were screened by using ANOVA and multivariate logistic regression. A nomogram was generated using clinical risk factors and the radiomic signature. The calibration curve and receiver operator characteristic (ROC) curve were used to confirm the nomogram's performance in the training and test sets. The clinical usefulness of the nomogram was evaluated by decision curve analysis (DCA). Furthermore, a testing cohort was used to validate the model. Results: The radiomics signature consisted of 21 features, and the nomogram model included the radiomics signature and the MR-reported lymph node status. The model showed good calibration and discrimination. The model yielded areas under the ROC curve (AUC) in the training cohort, specificity, and sensitivity of 0.930, 0.930 and 0.875. In the test cohort, the model yielded AUC, specificity and sensitivity of 0.883, 0.889 and 0.800. DCA indicated that the nomogram model was clinically useful. Conclusion: The MR-based radiomics nomogram model may be used to predict cervical lymph node metastasis of laryngeal cancer preoperatively. MR-based radiomics could serve as a potential tool to help clinicians make an optimal clinical decision.

[A case report of epidural abscess caused by acute frontal sinusitis].

Epidural epidural abscess is usually secondary to acute frontal sinusitis and osteomyelitis of the frontal bone. Nose-derived intracranial connplications are less common than otogenic ones, and infections caused by nasal and sinus trauma, foreign bodies and surgery are more common than those caused by inflammation alone. The frontal lobe abscess caused by frontal sinusitis is more common in brain abscess with nasal intracranial complications.

[Analysis of serum inhaled allergens in children with adenoid hypertrophy in Yantai area].

Objective:The results of the detection of the serum inhalant allergen in children with adenoid hypertrophy in Yantai were analyzed, and the common inhalant allergens and their distribution in the children with adenoid hypertrophy were found. Method:Serum inhaled allergen specific IgE（sIgE） was measured in 590 cases of adenoid hypertrophy from Nov 2017 to Oct 2018 by Symer allergen detection system, and stratified according to sex, age and visiting season. The distribution of inhaled allergens in serum of children with adenoid hypertrophy was described. Result:The positive rate of serum inhaled allergens in children with adenoid hypertrophy in Yantai area was 34.07%. Among them the most common inhaled allergens were dust mite（19.66%）, dust mite（18.98%） and the mixed mold（17.97%）. The positive degree of allergen in children with adenoid hypertrophy was mild（93 cases）, moderate（88 cases）, and severe（20 cases）. 76 cases were positive for single allergens, 79 cases were positive for 2 allergens, and 56 cases were positive for three or more allergens. Stratified study showed that there was no significant difference in the positive rate of inhaled allergens between male and female children（P>0.05）, but the positive rate of mixed mold and animal dandruff allergens in male children was higher than that in female children（P<0.05）. There was no significant difference in the positive rate of inhaled allergens between pre-school and school-age children（P>0.05）, and there was no significant difference in the positive rate of inhaled allergens in different seasons（P>0.05）. Conclusion:Dust mite, dust mite and mildew mixture were the most common inhaled allergens in children with adenoid hypertrophy in Yantai area. The positive degree of serum allergens in children with adenoid hypertrophy was mild to moderate, and most of the children were allergic to two kinds of allergens. Male children were more susceptible to mold mixing and animal dandruff. There was no significant difference in age and seasonal distribution of common inhaled allergens.