[Clinicopathological features of thyroid-like low-grade nasopharyngeal papillary adenocarcinoma].

Objective: To investigate the clinicopathological features, immunophenotype and gene alterations of thyroid-like low-grade nasopharyngeal papillary adenocarcinoma (TL-LGNPPA). Methods: Fifteen case of TL-LGNPPA diagnosed at Zhejiang Cancer Hospital (5 cases) and the First Affiliated Hospital, Zhejiang University School of Medicine (10 cases) from November 2011 to August 2020 were collected. Clinical and pathological examinations, immunohistochemical staining and next-generation sequencing were performed. The clinicopathological and molecular characteristics were summarized, and relevant literature was reviewed. Results: Fifteen patients were identified and included. Their median age was 36 years (range, 20-60 years). The male-female ratio was 1.0∶1.1. The most common symptoms were epistaxis and nasal obstruction. The neoplasms were located on the roof of the nasopharynx or the posterior margin of the nasal septum. The pathological features included complex papillary and glandular structures mainly composed of single or pseudostratified cubic and columnar cells, with mild to moderate cytological atypia. In some cases, spindle cell features, nuclear grooves, ground glass nuclei, squamous metaplasia, or scattered psammoma bodies were identified. In addition, nuclear polar reversal cells, hobnail cells and micropapillary structures were found, but have not been reported in previous literature. Immunohistochemistry showed that the tumor cells were diffusely positive for TTF1, CK7, vimentin and CKpan; focally positive for p40, CK5/6 and p16; and negative for Tg, NapsinA, CK20, CDX2, S-100 and PAX8. The Ki-67 positive rates ranged from 1% to 20% and were≤10% in thirteen cases (13/15). EBER in situ hybridization was negative in all cases. DNA sequencing of 6 specimens was performed and all specimens were found harboring gene mutations (EWSR1, SMAD2, ROS1, JAK3, GRIN2A, ERRCC5, STAT3, and TET2), but no hot spot gene alterations were found. No MSI-H and MMR related gene changes were detected. All tumors showed low tumor mutation burden. All 15 patients underwent endoscopic surgery, and only 1 of them underwent radiotherapy postoperatively. All patients were recurrence free and alive at the end of follow-up periods (range: 23 to 129 months). Conclusions: TL-LGNPPA is a rare indolent tumor of the nasopharynx and exhibits a unique morphology and immunophenotype. Endoscopic resection is an effective treatment for TL-LGNPPA with excellent overall prognosis.

[Clinical features and prognoses of re-operated patients for persistent/recurrent papillary thyroid carcinoma].

Objective: To investigate the clinicopathological characteristics and the survival of re-operated patients for persistent/recurrent papillary thyroid carcinoma (PTC) and risk factors for re-recurrence after the second operation. Method: A retrospective analysis of 69 cases underwent re-operation for persistent/recurrent PTC in Sichuan Cancer Hospital from January 2010 to December 2016 was performed. There were 21 males and 48 females, aged 14-85 (44.8) years old. According to the imaging after initial treatment, they were divided into a recurrence group (42 cases) and a persistent disease/residual group (27 cases). The positive rates of ipsilateral paratracheal lymph node metastases at re-operation were calculated and compared by chi-square test. Patients were divided into different subgroups according to potential risk factors for re-recurrence. Kaplan-Meier (K-M) method was used for survival analysis. Results: The positive rate of ipsilateral paratracheal lymph node metastasis in recurrence group (15/42, 35.7%) was significantly lower than that in the persistent disease/residual group (17/27, 63.0%) (χ2=4.91, P<0.05). The follow-up period after re-operation was 60-104 months, with a median of 66 months, and 8 patients were lost to follow-up. Permanent hypoparathyroidism occurred in 2 cases (2.9%) and permanent recurrent laryngeal nerve palsy in 1 case (1.4%). Twenty patients had structural recurrences and/or distant metastases. The 5-year disease-specific survival rate was 92.8% and the 5-year recurrence-free survival rate was 68.1%. Survival analysis was performed on risk factors such as age≥55 years old, recurrent tumor diameter ≥4 cm, number of positive lymph nodes ≥ 10, and obvious extracapsular invasion (ENE). Among them, age and diameter of recurrent tumor had significant influences on recurrence-free survival rate (χ2 was 6.36, 8.17, respectively, both P values<0.05). There was a statistically significant difference in recurrence-free survival rates between ENE(+) group and ENE(-) group (χ2=5.52, P<0.05). Conclusion: For the re-operated patients due to persistence/ recurrence PTC, attention should be paid to protecting the parathyroid gland and recurrent laryngeal nerve during re-operation. Timely and effective postoperative follow-up for patients aged ≥ 55 years, with recurrent tumor diameter ≥ 4 cm and ENE(+), can significantly improve their prognoses.

[Comparison of three kinds of free flaps used in patients with oral and oropharyngeal tumors].

Objective: To compare the recovery and quality of life of patients with oral and oropharyngeal tumors treated with three kinds of free soft tissue flaps. Methods: The clinical data of 103 patients, including 66 males and 37 females, aged 26-74 years, who underwent primary repair of defects after resection of oral and oropharyngeal tumors in Sichuan Tumor Hospital from July 2014 to August 2020 were analyzed. Anterolateral thigh flap (ALTF) was used in 43 patients, radial forearm free flap (RFFF) in 45 patients, and lateral arm free flap (LAFF) in 15 patients. Postoperative qualities of life of patients were evaluated by the university of Washington quality of life questionnaire and oral health impact scale (HIP-14 Chinese edition). SPSS 23.0 software was used for statistical analysis. Results: The T staging of RFFF or LAFF group was significantly lower than that of ALTF group (P<0.05). There was no significant difference in mean flap areas between ALTF group ((55.87±27.38) cm2) and LAFF group ((49.93±19.44) cm2), while RFFF group had smaller mean flap area ((33.18±6.05) cm2) than ALTF group (t=5.311, P<0.001) and LAFF group (t=3.284, P=0.005). In terms of oral functions including swallowing, mastication, taste and spitmouth, there were no significant differences between LAFF group and RFFF group (P>0.05), but both groups had better oral functions than ALTF group (P<0.05). There was no significant difference in appearance scores between LAFF group (75(75, 75)) and ALTF group (75(75,75) vs.75(75,75),Z=-1.532, P=0.126), and both groups had higher scores than RFFF group (50(50, 75),Z values were -3.447 and -3.005 respectively, P<0.05). RFFF group had higher speech score (100(67, 100)) than LAFF group (67(50, 76),Z=-2.480, P<0.05) and ALTF group (67(33, 67),Z=-5.414, P<0.05). ALTF group had lower mean score of quality of life than RFFF group [72(56,77) vs.79(69, 89),Z=-3.070, P<0.05), but there was no statistical difference in the mean scores of qualities of life between ALTF group and LAFF group (Z=1.754, P=0.079). According to the evaluation of oral health impact scale (HIP-14 Chinese version) 1 year after surgery, individual item scores and the average score of all items in ALTF group were lower than those in RFFF and LAFF groups (P<0.05), with no significant difference between RFFF group and LAFF group (P>0.05). Conclusions: RFFF has unique advantages for small tissue defects, while ALTF is suitable for large tissue defects, such as buccal penetrating defect, whole tongue and near whole tongue defect, and LAFF is a compromise choice between ALTF and RFFF. ALTF is inferior to RFFF and LAFF in oral functional reconstruction, including swallowing, chewing, taste and spittle. ALTF and LAFF are superior to RFFF in postoperative appearance.

[Posterior sternocleidomastoid border approach of gasless transaxillary endoscopic thyroidectomy in patients with papillary thyroid carcinoma: comparison with sternocleidomastoid fascia approach].

Objective: To examine the posterior sternocleidomastoid border approach which elevated whole sternocleidomastoid in gasless transaxillary endoscopic thyroidectomy. Methods: The clinical data of 46 patients with papillary thyroid carcinoma treated with gasless transaxillary endoscopic thyroidectomy from May 2019 to June 2020 at Department of Head and Neck Surgery, Sichuan Cancer Hospital was analyzed retrospectively. There were 9 males and 37 females, aged (38.6±12.0) years (range: 19 to 74 years). Fourteen and 32 cases performed posterior sternocleidomastoid border and sternocleidomastoid fascia approach, respectively. Comparative analysis were performed on clinical characters, surgical outcomes, postoperative complications, postoperative pain score, and quality-of-life of postoperative 1 month by t test, Wilcoxon rank sum test, Fisher exact test and χ2 test,respectively. Resuts Complete exposure of central compartment was higher (11/14 vs. 34.4%(11/32),χ²=7.624, P=0.006), more lymph nodes was retrieved (4.2±2.9 vs. 2.0±2.5, t=2.663, P=0.011) in posterior sternocleidomastoid border approach. There were no significant differences between groups in postoperative complications such as recurrent laryngeal nerve palsy (1/14 vs. 3.1%(1/32), P=0.521) and transient hypoparathyroidism (0 vs. 6.2%(2/32), P=1) and pains and quality-of-life. Conclusion: Posterior sternocleidomastoid border approach of gasless transaxillary endoscopic thyroidectomy is safe and reliable and has the advantage of central compartment dissection without increasing trauma.

MiR-34a-5p inhibition attenuates LPS-induced endothelial cell injury by targeting FOXM1.

OBJECTIVE: This study aims to investigate the role of miR-34a-5p in the regulation of lipopolysaccharide (LPS)-induced injury of vascular endothelial cells (ECs). MATERIALS AND METHODS: Human umbilical vein ECs (HUVECs) were exposed to LPS to stimulate endothelial injury in vitro. miRNA microarray analysis was carried out to identify miR-34a-5p expression in HUVECs. MTT and flow cytometry analyses were used to determine cell viability and apoptosis rate, respectively. Furthermore, enzyme-linked immunosorbent assay (ELISA), qRT-PCR, and Western blot were used to examine the factors involved in inflammation and their relative gene expression. Additionally, Matrigel-based tube formation assay was carried out to assess the vasculogenic activity of HUVECs. Luciferase reporter assay was used to analyze the possible relationship between miR-34a-5p and FOXM1. RESULTS: MiR-34a-5p expression was significantly enhanced in HUVECs after 24 h of LPS treatment. LPS treatment led to a dramatic inhibition of cell viability, enhanced apoptosis, increased production of pro-inflammatory cytokines, and inhibited the vasculogenic activity of HUVECs. MiR-34a-5p inhibitor attenuated LPS-induced damage. MiR-34a-5p directly inhibited the expression of FOXM1, and its overexpression alleviated the protective effect of FOXM1 on cell viability, apoptosis, inflammation factor production, and vasculogenic activity. The activity of the NRF2/HO-1 pathway was inhibited by miR-34a-5p, possibly via FOXM1. CONCLUSIONS: MiR-34a-5p inhibition attenuates LPS-induced EC injury by targeting FOXM1 via activation of the NRF2/HO-1 pathway.

New scheme for the preparation and use of artificial cerebrospinal fluid.

This study aimed to explore a set of simplified schemes for the preparation and application of artificial cerebrospinal fluid (ACSF) to improve the experiment efficiency and neurosafety of ACSF. We prepared ACSF into parts A and B, according to the cerebrospinal fluid (CSF) data in rabbits. They were mixed in equal volumes to form ACSF, continous foaming with mixture gas (95% O2 and 5% CO2). Sampling inspection showed the chemical stability of ACSF in the three months after preparation. However, it needed to be kept continous foaming, as pH is correlated to the solubility of CO2. We further improved the application scheme by sealing the foamed ACSF in infusion bags filled with mixture gas, which could keep the pH stable for 24 hours. It was helpful in promoting the progress of clinical and experimental research relating to ACSF.

[Factors related to thyroid carcinoma in Zhejiang province: a matched case-control study].

Objective: To explore the influencing factors related to thyroid carcinoma. Methods: Matched by sex, age and original residential areas, 659 pairs of cases and controls were recruited and studied. Methods including both single factor analysis and multivariate conditional logistic regression analysis were carried out to identify the influencing factors. Results: Multivariate conditional logistic regression analysis showed that higher education, being diabetic, alcohol intake, tea drinking, occupational physical activity and the frequency of eating fishes/eggs etc., were potentially protective to thyroid carcinoma. Depression, personal history of CT examination and less salt intake seemed to be risk factors on thyroid carcinoma. For males, factors as alcohol intake, tea drinking, occupational physical activity and frequent egg-eating appeared protective. For females, higher education, diabetes, tea drinking, occupational physical activity, frequent consumption of fishes/eggs, short duration of menstruation appeared as possibly protective. Conclusion: Higher education, diabetes, alcohol intake, tea drinking, occupational physical activity, frequent consumption of fishes/eggs, depression, personal history of CT examination and less salt intake served as potential influencing factors to thyroid carcinoma.

[Peripheral blood circulating tumor cells in local advanced head and neck squamous cell carcinoma].

Objective: To investigate the value of detecting circulating tumor cells (CTCs) in patients with local advanced head and neck squamous cell carcinoma (LAHNSCC). Methods: Twenty cases of LAHNSCC and eight healthy cases as the negative control were collected. The clinicopathological factors were evaluated. The LAHNSCC CTCs were enriched by specific antibody nanofluidic chip immunoassay using CytoSorter CTCs sorting system. LAHNSCC CTCs were identified by immunofluorescence staining. The relationships between CTCs and the clinicopathological features of LAHNSCC were analyzed. The numbers of CTCs were monitored and compared two weeks after inductive chemotherapy and at the end of the treatment. Results: CTCs were detect in 15 (75%) 20 patients with LASHNCC, with an average number of 22.4 CTCs. There was a correlation between the numbers of CTCs and age or N staging (P<0.05). Among the 15 cases with CTCs, 13 cases received inductive chemotherapy, for whom CTCs were detected again after inductive chemotherapy in all of these 13 patients, with an average number of 9.5 CTCs. Ten of the fourteen cases (71.4%) were still CTCs detected After whole treatments CTCs were detected in 14 patients, of them, 10 (71.4%) patients showed positive CTCs, with an average 1.6 CTCs. The numbers of CTCs decreased after either inductive chemotherapy or the whole treatment. The number of detected CTCs after whole treatment decreased nearly to background levels. Conclusions: CTCs have a high detection rate in the peripheral blood of patients with LAHNSCC, especially in patients ≥60 years old and with ≥ N2 stage before treatment. Real-time detection of dynamic change of CTCs may assist to evaluate therapeutic effect.

[Progress in research of thyroid carcinoma related gene mutation and epigenetics].

Thyroid cancer is one of the most common endocrine malignant tumors, and its molecular pathogenesis is also a process of multiple genes involved in many steps of carcinogenesis. With the development of molecular biology technology, a variety of related gene mutations and epigenetic phenomena have been found in thyroid cancer tissues. It is helpful to understand the latest progress in the research of the gene mutation and epigenetics of thyroid cancer for its early diagnosis, prevention and the development of targeted drugs.

[Clinicopathological characteristics of papillary thyroid microcarcinoma and risk factors for central lymph node metastasis].

Objective: To analyze the clinicopathological characteristics of papillary thyroid microcarcinoma (PTMC) and risk factors for central lymph node metastasis(CLNM) in PTMC. Methods: The data of 900 patients with PTMC initially treated in our hospital from January 2004 to December 2015 were retrospectively analyzed. Chi-square test and Logistic regression analysis were performed to determine the risk factors for CLNM. Results: CLNM affected 162 (22.9%) of 707 patients treated with central lymph node dissection. Age, maximum tumor size, multifocality, bilaterality, and extracapsular spread (ECS) were significantly correlated with CLNM (all P<0.01). Age<45 years, maximum tumor size>5 mm, multifocality, bilaterality, and extracapsular spread were independently correlated with CLNM. Conclusion: A prophylactic central lymph node dissection should be considered in PTMC patients with age<45 years, maximum tumor size>5 mm, multifocality, bilaterality, and extracapsular spread.

Experimentally simulating quantum walks with self-collimated light.

In self-collimated photonic crystal, periodically arranged air holes of sub-wavelength scale provide flattened equi-frequency curves perpendicular to the ΓM direction, which allow light or photons propagating in a quasi-uniform medium without diffraction. Here we for the first time experimentally simulate four-step single-photon discrete time quantum walks with classical light in such a photonic crystal chip fabricated on silicon-on-insulator. Similarities between theoretical expectations and experimental results are higher than 0.98. The functional area is compact and can be extended to construct more complicated linear quantum circuits.

Self-reported Sleep Improvement in Buprenorphine MAT (Medication Assisted Treatment) Population.

This is a prospective, naturalistic study to evaluate patient's report on sleep and depression in early recovery while receiving buprenorphine in Medication Assisted Treatment (MAT). 40 Subjects entering into MAT with buprenorphine/naloxonefor opioid dependence disorder were recruited. No change of concurrent treatment was made. Subjects were administered Sleep Scale from the Medical Outcomes Study (MOS-Sleep), a 5-item Supplemental Sleep Scale (SSS), and the Beck Depression Inventory II (BDI-II). The measures were administered at day 0 (baseline), 30, 60 and 90 days. The result showed that patients reported significant progressive improvements in three MOS-Sleep subscales: sleep disturbance, sleep indices I and II. The mean scores of SLPD4 (Sleep disturbance) at day 0, 30, 60, 90 were 62.4, 53.2, 53.3, and 48.4 respectively (p=0.0029). Similarly, subscores of SLP6 (Sleep Problem Index I) and SLP 9 (Sleep Problem Index II) were also significantly decreased over time (P=0.038 for SLP6 and p=0.007 for SLP9). BDI-II depression scores improved from "Moderate depression" at baseline to "Mild depression". The mean BDI score decreased from 24.2 to 17.0 after 90 days of treatment. Findings suggest that subjects reported improvement in both sleep and depression after initiating MAT with buprenorphine/naloxone.

Conservation and population genetic diversity of Curcuma wenyujin (Zingiberaceae), a multifunctional medicinal herb.

Curcuma wenyujin is an important multifunctional medicinal herb in China. Currently, populations of C. wenyujin are decreasing, and wild individuals have almost disappeared from their natural habitats. Moreover, little is known regarding the molecular characteristics of this plant. In this study, we investigated the genetic diversity and variation of five populations of C. wenyujin, using ran-dom amplified polymorphic DNA (RAPD) and inter-simple sequence repeat (ISSR) markers. We found that the percentages of polymorphic loci (PPL) at the species level (98.25% by RAPD and 100% by ISSR) were significantly higher than those at the population level (66.32% by RAPD and 67.14% by ISSR). The highest values of PPL, expected heterozygosity, and Shannon's information index were in Pop1, while the lowest values were in Pop2. Both DNA markers revealed a short genetic distance between Pop1 and Pop2 (0.1424 by RAPD and 0.1904 by ISSR). Phylogenetic trees produced similar results, with Pop1, Pop2, and Pop5 in one group and Pop3 and Pop4 in another. There were no significant correlations between their genetic distances and their geographical distances. The highest genetic diversity was in Pop1 and the lowest was in Pop2, and genetic diversity at the species level was relatively low, but much higher than that at the population level. We recommended the establishment of a germplasm bank, in situ con-servation, and propagation of wild individuals. The present study will improve the evaluation, protection, and utilization of the population resources of C. wenyujin.

Relevance of E-cadherin expression to EGFR-TKI molecular targeted therapy sensitivity/resistance and its clinical significance.

We examined the effect of E-cadherin expression on epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) molecular targeted therapy sensitivity/resistance. We treated MCF-7, MDA-MB-231, T24, SiHa, H460, SK-HEP-1, MHCC97-H, and THP-1 cells with the EGFR-TKIs PD153035 and gefitinib, and then tested the drug-resistance and sensitivity using the MTT method, calculated IC50 values for each cell line, and compared the results to E-cadherin content. The MTT assay was used to determine the survival rates of MCF-7, MDA-MB-231, T24, SiHa, H460, SK-HEP-1, MHCC97-H, and THP-1 cells upon the action of EGFR-TKI (PD153035, gefitinib). For PD153035, the IC50 in MCF-7, MDA-MB-231, T24, and SiHa cells differed from that of H460, SK-HEP-1, MHCC97-H, and THP-1 (P < 0.05). Following gefitinib treatment, the IC50 values of MCF-7, MDA-MB-231, T24, and SiHa cells differed from those of H460, SK-HEP-1, MHCC97-H, and THP-1 cells (P < 0.01). The survival rate of MCF-7, MDA-MB-231, T24, and SiHa cells clearly decreased with increasing drug concentration, indicating the cells were sensitive to the drugs and that E-cadherin expression was positive; however, H460, SK-HEP-1, MHCC97-H, and THP-1 cells showed no significant decreased with increasing drug concentration, indicating that they were resistant to the drugs and that E-cadherin expression was negative. The survival rate of epithelial tumor cells through the action of EGFR-TKI is related to E-cadherin expression. E-cadherin may play a significant role in the sensitivity regulation of EGFR molecular targeting treatment. E-cadherin may provide important clues for selecting proper EGFR-TKI molecular targeting treatment.

Angled cavity photonic crystal laser diodes with tilted sidewalls for improving far-field patterns.

Angled laser diodes based on the longitudinal photonic band crystal (PBC) waveguide are first proposed and fabricated at a wavelength of 905 nm. Tilted sidewalls are utilized to reflect the light downward, thus enlarging the transverse mode size. In the experiment, continuous wave (CW) output power of 630 mW/facet is achieved, and stable and narrow divergence angles are obtained in the fast and slow axes, simultaneously. The transverse angle is reduced by 44% compared with that of the conventional broad area (BA) laser based on the same wafer, and the lateral angle is only 1.65° with on-axis main-lobe emission. This device shows a promising future for laser emission with ultra-narrow divergence and easy fabrication.

Fluorescent quantitative PCR of Mycobacterium tuberculosis for differentiating intestinal tuberculosis from Crohn's disease.

Intestinal tuberculosis (ITB) and Crohn's disease (CD) are granulomatous disorders with similar clinical manifestations and pathological features that are often difficult to differentiate. This study evaluated the value of fluorescent quantitative polymerase chain reaction (FQ-PCR) for Mycobacterium tuberculosis (MTB) in fecal samples and biopsy specimens to differentiate ITB from CD. From June 2010 to March 2013, 86 consecutive patients (38 females and 48 males, median age 31.3 years) with provisional diagnoses of ITB and CD were recruited for the study. The patients' clinical, endoscopic, and histological features were monitored until the final definite diagnoses were made. DNA was extracted from 250 mg fecal samples and biopsy tissues from each patient. The extracted DNA was amplified using FQ-PCR for the specific MTB sequence. A total of 29 ITB cases and 36 CD cases were included in the analysis. Perianal disease and longitudinal ulcers were significantly more common in the CD patients (P<0.05), whereas night sweats, ascites, and circumferential ulcers were significantly more common in the ITB patients (P<0.05). Fecal FQ-PCR for MTB was positive in 24 (82.8%) ITB patients and 3 (8.3%) CD patients. Tissue PCR was positive for MTB in 16 (55.2%) ITB patients and 2 (5.6%) CD patients. Compared with tissue FQ-PCR, fecal FQ-PCR was more sensitive (X2=5.16, P=0.02). We conclude that FQ-PCR for MTB on fecal and tissue samples is a valuable assay for differentiating ITB from CD, and fecal FQ-PCR has greater sensitivity for ITB than tissue FQ-PCR.