[Treatment and prognosis analysis of perineural invasion on sinonasal adenoid cystic carcinoma].

Objective: To analyze the efficacy of sinonasal adenoid cystic carcinoma (ACC) with perineural invasion (PNI), and explore the prognostic value of PNI on sinonasal adenoid cystic carcinoma. Methods: The clinical data of 105 patients with sinonasal ACC admitted to Cancer Hospital, Chinese Academy of Medical Sciences from January 2000 to December 2016 were retrospectively reviewed. All patients were restaged according to American Joint Committee on Cancer 8th edition. Follow-up visits were conducted to obtain information of treatment failure and survival outcome. The Log rank test was used for univariate analysis of prognostic factors, and Cox regression model was used for multivariate prognostic analysis. Results: The maxillary sinus (n=59) was the most common primary site, followed by the nasal cavity (n=38). There were 93 patients with stage Ⅲ-Ⅳ. The treatment modalities included surgery alone (n=14), radiotherapy alone (n=13), preoperative radiotherapy plus surgery (n=10), and surgery plus postoperative radiotherapy (n=68). The median follow-up time was 91.8 months, the 5-year local control (LC), distant metastasis-free survival (DMFS), progression-free survival (PFS), and overall survival (OS) rates were 72.6%, 73.0%, 52.9% and 78.0%, respectively. There were 33 patients (31.4%) with PNI-positive. The 5-year DMFS, PFS, and OS rates of PNI-positive group were 53.7%, 29.4% and 56.5%, respectively, which were significantly inferior to those of PNI-negative group (80.8%, 63.0% and 86.8%, respectively, P<0.05), while there was no significant difference in the 5-year LC rate between both groups (64.5% vs 76.5%, P=0.273). The multivariate Cox regression analysis showed PNI was one of the poor prognostic factors of DMFS (HR=3.514, 95%CI: 1.557-7.932), PFS (HR=2.562, 95%CI: 1.349-4.866) and OS (HR=2.605, 95%CI: 1.169-5.806). Among patients with PNI-positive, the 5-year LC, PFS and OS rates of patients received surgery combined with radiotherapy were 84.9%, 41.3% and 72.7%, respectively, which were significantly higher than 23.3%, 10.0% and 26.7% of patients receiving surgery or radiotherapy alone (P<0.05). Conclusion: The presence of PNI increases the risk of distant metastasis in patients with sinonasal ACC. Compared with patients with PNI-negative, the prognosis of patients with PNI-positive is relatively poor, and surgery combined with radiotherapy for PNI-positive sinonasal ACC results in good clinical outcomes.

[Long-term outcomes and failure patterns of definitive radiotherapy for cervical esophageal carcinoma].

Objective: To evaluate the long-term outcomes, failure patterns and prognostic factors of definitive radiotherapy in patients with cervical esophageal carcinoma (CEC). Methods: We retrospectively reviewed the clinical data of 148 CEC patients who treated with definitive radiotherapy in Cancer Hospital of Chinese Academy of Medical Sciences from January 2001 to December 2017. The median radiation dose was 66 Gy (59.4-70 Gy) and 33.1% of patients received concurrent chemotherapy. The Kaplan-Meier method was used to calculate survival rates. The log rank test was used for survival comparison and univariate prognostic analysis. The Cox model was used for multivariate prognostic analysis. Results: The median follow-up time was 102.6 months. The median survival time, 2- and 5-year overall survival (OS) were 22.7 months, 49.9% and 28.3%. The median, 2- and 5-year progression-free survival were 12.6 months, 35.8% and 25.8%. The 2- and 5-year locoregional recurrence-free survival were 59.1% and 50.8%. The 2- and 5-year distant metastases-free survival were 74.6% and 65.9%. Multivariate analysis showed that EQD(2)>66 Gy was the only independent prognostic indicator for OS (P=0.040). The median survival time and 5-year OS rate significantly improved in patients who received EQD(2)>66 Gy than those who received≤66 Gy (31.2 months vs. 19.2 months, 40.1% vs. 19.1%, P=0.027). A total of 87 patients (58.8%) developed tumor progression. There were 50 (33.8%), 23 (15.5%) and 39 (26.4%) patients developed local, regional recurrence and distant metastases, respectively. Eleven patients (7.4%) underwent salvage surgery, and the laryngeal preservation rate for entire group was 93.9%. Conclusions: Definitive radiotherapy is an effective treatment for cervical esophageal carcinoma with the advantage of larynx preservation. Local recurrence is the major failure pattern. EQD(2)>66 Gy is associated with the improved overall survival.

[Mouse models for human colorectal cancer with liver metastasis].

Objective: To established Apc(loxp/loxp)+Kras(LSL-G12D/-)+Smad4(loxp/loxp) transgenic mouse model that mimick the occurrence and development of human sporadic colorectal cancer(CRC) and its liver metastasis. Methods: C57BL/6-Apc(tm1Tyj)/J(Apc(loxP)), B6.129S4-Kras(tm4Tyj)/J(Kras(LSL-G12D)), 129S6-Smad4(tm2.1Cxd)/J(Smad4(loxP)) and C57BL/6J mice were crossed, and genotype with Apc(loxP/loxP)+Kras(LSL-G12D/-)and Apc(loxP/loxP)+Kras(LSL-G12D/-)+Smad4(loxP/loxP)were generated. Genotypes of the mice were identified by PCR and real-time quantitative PCR. The mice were divided into Apc(loxP/loxP)+Kras(LSL-G12D/-)+Smad4(loxP/loxP) group (n=20) and Apc(loxP/loxP)+Kras(LSL-G12D/-)group(n=24). Lentivirus expressing Cre enzyme and IRES-luciferase were injected into the submucosa of colon or rectum of the transgenic mice under colonoscopy. Intraabdominal injection of D-luciferase into mice every 4 weeks, imaging with small animal in vivo imaging system(IVIS). The tumor size, tumorigenesis rate and metastasis ratio were analyzed. At the end of the 20th week, the colorectal lesions and metastatic tissues of mice were stained with hematoxylin-eosin(HE) and the pathological changes were observed under microscope. Results: Apc(loxp/loxp)+Kras(LSL-G12D/-)+Smad4(loxp/loxp) and Apc(loxp/loxp)+Kras(LSL-G12D/-)transgenic mice were successfully bred. The colorectal stem cells of the transgenic mouse mutated leading tumor lesion and liver metastatic under the induction of Lentivirus(Cre-IRES-luciferase). The primary and metastatic foci of colorectal carcinoma and liver metastasis in mice were proved to be adenocarcinoma and liver metastatic carcinoma by histopathological examination. The primary tumor size inApc(loxP/loxP)+Kras(LSL-G12D/-)+Smad4(loxP/loxP) group and Apc(loxP/loxP)+Kras(LSL-G12D/-)group was(3.52±0.26) and(3.45±0.20)mm, respectively,without significant difference(t=0.872, P=0.388).The tumorigenesis rate was 70.0% and 50.0% respectively, and there was no significant difference between the two groups(χ(2)=0.440, P=0.507). The metastasis rate of two groups were 58.3% and 8.3%respectively(Fisher's exact test, P=0.027). Conclusions: In this study, the colorectal carcinogenesis and its spontaneously metastasis to the liver of CRC were induced by Lentivirus(Cre-IRES-luciferase) in our established transgenic mice,which successfully simulated the occurrence and development of human sporadic CRC and its liver metastasis.

Risk assessment of dengue fever in Zhongshan, China: a time-series regression tree analysis.

Dengue fever (DF) is the most prevalent and rapidly spreading mosquito-borne disease globally. Control of DF is limited by barriers to vector control and integrated management approaches. This study aimed to explore the potential risk factors for autochthonous DF transmission and to estimate the threshold effects of high-order interactions among risk factors. A time-series regression tree model was applied to estimate the hierarchical relationship between reported autochthonous DF cases and the potential risk factors including the timeliness of DF surveillance systems (median time interval between symptom onset date and diagnosis date, MTIOD), mosquito density, imported cases and meteorological factors in Zhongshan, China from 2001 to 2013. We found that MTIOD was the most influential factor in autochthonous DF transmission. Monthly autochthonous DF incidence rate increased by 36·02-fold [relative risk (RR) 36·02, 95% confidence interval (CI) 25·26-46·78, compared to the average DF incidence rate during the study period] when the 2-month lagged moving average of MTIOD was >4·15 days and the 3-month lagged moving average of the mean Breteau Index (BI) was ⩾16·57. If the 2-month lagged moving average MTIOD was between 1·11 and 4·15 days and the monthly maximum diurnal temperature range at a lag of 1 month was <9·6 °C, the monthly mean autochthonous DF incidence rate increased by 14·67-fold (RR 14·67, 95% CI 8·84-20·51, compared to the average DF incidence rate during the study period). This study demonstrates that the timeliness of DF surveillance systems, mosquito density and diurnal temperature range play critical roles in the autochthonous DF transmission in Zhongshan. Better assessment and prediction of the risk of DF transmission is beneficial for establishing scientific strategies for DF early warning surveillance and control.

Molecular Weight, Protein Binding Affinity and Methane Mitigation of Condensed Tannins from Mangosteen-peel (Garcinia mangostana L).

The objectives of this study were to determine the molecular weight of condensed tannins (CT) extracted from mangosteen (Garcinia mangostana L) peel, its protein binding affinity and effects on fermentation parameters including total gas, methane (CH4) and volatile fatty acids (VFA) production. The average molecular weight (Mw) of the purified CT was 2,081 Da with a protein binding affinity of 0.69 (the amount needed to bind half the maximum bovine serum albumin). In vitro gas production declined by 0.409, 0.121, and 0.311, respectively, while CH4 production decreased by 0.211, 0.353, and 0.549, respectively, with addition of 10, 20, and 30 mg CT/500 mg dry matter (DM) compared to the control (p<0.05). The effects of CT from mangosteen-peel on in vitro DM degradability (IVDMD) and in vitro N degradability was negative and linear (p<0.01). Total VFA, concentrations of acetic, propionic, butyric and isovaleric acids decreased linearly with increasing amount of CT. The aforementioned results show that protein binding affinity of CT from mangosteen-peel is lower than those reported for Leucaena forages, however, the former has stronger negative effect on IVDMD. Therefore, the use of mangosteen-peel as protein source and CH4 mitigating agent in ruminant feed requires further investigations.

Exhaustive swimming exercise related kidney injury in rats - protective effects of acetylbritannilactone.

The aim of this study was to investigate the protective effects of acetylbritannilactone (ABL) on renal injury induced by acute exhaustive exercise in the rat. The exhaustive exercise induced kidney injury in rats was established by exhaustive swimming (ES). ABL (26 mg/kg) or polyglycol (control) were administrated orally by gastric gavage 24 h before training. Renal function, biochemical index, renal histopathological change, oxidative stress indices, renal cell apoptosis and inflammatory molecules were checked after ES, for 6 h and 24 h. It was found that immediately after exhaustive swimming, the serum urea and creatinine were significantly higher in ES rats, and the same for serum creatine kinase. All the values were reduced in the ES rats treated with ABL. The increase of superoxide dismutase activity and decrease of malondialdehyde content in the kidney were found in rats with ABL treatment. Tubular cell apoptosis at different time points after ES were significantly reduced by the ABL treatment. The increased expression of TNF-α and NF-κB induced by ES was also significantly decreased by ABL treatment. Our results suggest that ABL protects rats from overtraining-induced kidney injury by inhibiting renal cell apoptosis and suppressing oxidative-stress generation and inhibiting inflammation.

Long non-coding RNA ENST00000434223 inhibits the progression of renal cancer through Wnt/hygro-catenin signaling pathway.

OBJECTIVE: The purpose of this study was to determine the function of long non-coding RNA (LncRNA) ENST00000434223 (Lnc ENST) in renal carcinoma, and to explore the potential molecular mechanism. PATIENTS AND METHODS: Quantitative Real-Time-Polymerase Chain Reaction (qRT-PCR) was used to detect the expressions of lncRNA ENST00000434223 and Wnt/ß-catenin pathway-related mRNAs in tissues and cells of renal cancer. Chi-square test was performed to figure out the relationship between lncRNA ENST00000434223 and clinic-pathologic features of renal cancer patients. Besides, si-NC, si-ENST00000434223, pcDNA-NC and pcDNA-ENST00000434223 were transfected into renal cancer cells. The proliferative ability, metastasis and invasiveness of cells were detected using Cell Counting Kit-8 (CCK-8) and transwell assay, respectively. Lastly, the activation of the Wnt/hygro-catenin signal transduction pathway was evaluated by TOP/FOP Wnt Luciferase reporter assay and Western blot. RESULTS: The expressions of Wnt2b and ß-catenin were significantly increased in renal carcinoma, while E-cadherin was markedly down-regulated. Lowly expressed ENST00000434223 was involved in the poor prognosis of patients with renal cancer. In addition, down-regulating ENST00000434223 could enhance the viability, metastasis and invasiveness of renal cancer cells. However, overexpressing ENST00000434223 remarkably weakened the above cell functions. At the same time, interference or overexpression of ENST00000434223 could affect the expression level of proteins related to the Wnt/ß-catenin signal pathway. CONCLUSIONS: LncRNA ENST00000434223 inhibits the progression of renal cancer through the Wnt/shell-catenin signal pathway.

Electrochemical characteristics of amorphous silicon carbide film as a lithium-ion battery anode.

The electrochemical reactions of SiC film with Li+ have been investigated by electrochemical characterization and X-ray photoelectron spectroscopy. The SiC film is prepared by inductively-coupled-plasma chemical-vapor-deposition (ICP-CVD) technique and displays an amorphous state due to the low processing temperature (∼350 °C). An irreversible reaction of SiC with Li+ occurs with the formation of lithium silicon carbide (Li x Si y C) and elemental Si, followed by a reversible alloying/dealloying reaction of the elemental Si with Li+. The 500 nm SiC film shows an initial reversible specific capacity of 917 mA h g-1 with a capacity retention of 41.0% after 100 cycles at 0.3C charge/discharge current, and displays much better capacity retention than the Si film (5.2%). It is found that decreasing the SiC thickness effectively improves the specific capacity by enhancing the reaction kinetics but also degrades the capacity retention (for 250 nm SiC, its initial capacity is 1427 mA h g-1 with a capacity retention of 25.7% after 100 cycles). The better capacity retention of the 500 nm SiC anode is mainly because residual SiC exists in the film due to its incomplete reaction caused by its lower reaction kinetics, and it has high hardness and can act as a buffer matrix to alleviate the anode volume change, thus improving the mechanical stability and capacity retention of the SiC anode.

[Risk factors related to HIV new infections among men who have sex with men in a cohort study].

Objectives: To analyze and understand the risk factors related to HIV new infections among men who have sex with men (MSM). Methods: A longitudinal observational study among MSM was conducted to collect information on HIV related behaviors and sero-conversion. Univariate and multivariate generalized estimating equations (GEE) were used to discuss the risk factors for HIV new infection. Results: A total number of 4 305 MSM were followed during 2013-2015. Among those self-reported MSM who are seeking partners on the Interner tended to have higher proportion on receptive anal intercourse and consistent condom use during anal intercourse than the subgroups seeking their partners in gay bars or bathrooms. HIV incidence among followed MSM during the study period appeared as 4.3/100 person years, with adjusted RR (aRR) of HIV infection for receptive anal intercourse as group 2.20 (95% CI: 1.49-3.24) times than that of insertion anal intercourse group. Those who used rush-poppers (aRR=1.55, 95% CI: 1.10-2.17), unprotected anal intercourse (aRR=2.24, 95%CI: 1.62-3.08), and those with syphilis infection (aRR=2.95, 95%CI: 2.00-4.35) were also risk factors for HIV new infections. After controlling other factors, the relationship between the ways of seeking partners and HIV new infection was not statistical significant. Conclusion: Risk factors for HIV new infection among MSM appeared complex and interactive, suggesting that further studies are needed to generate tailored strategies for the prevention of HIV epidemic among MSM population.

Naloxone inhibits arrhythmias induced by coronary artery occlusion and reperfusion in anaesthetized dogs.

The intravenous administration of naloxone 2 min before coronary artery occlusion in anaesthetized dogs reduced the incidence and severity of cardiac arrhythmias during coronary occlusion (20 min) and reperfusion (120 min) in a dose-related manner. It also reduced the mortality. At a dose of 1 mg kg-1 (the maximum dose used in this study) naloxone abolished the appearance of the life threatening ventricular fibrillation (VF) and ventricular tachycardia (VT) and as a consequence all dogs in this group survived. The results suggest a possible involvement of endogenous opioid peptides in arrhythmogenesis during coronary occlusion and reperfusion in the dog.

Removal of known, abundant cDNA species by specific double-stranded cDNA synthesis-based subtraction.

An efficient and simple method for removing known, abundant cDNA species from the cDNA pool of highly differentiated cells is reported. The method involves preparation of sscDNA, followed by dscDNA-synthesis of known, abundant cDNA species led by specific primers and removal of the synthesized dscDNA with hydroxyapatite. By using this method, the globin cDNAs were reduced to less than 10(-5) of their original abundance. The results suggest that this method may facilitate the isolation of new genes from specific cells or tissues.

Morphine and (D-Ala2, NMe-Phe4, Gly-ol)-enkephalin increase the intracellular free calcium in isolated rat myocytes--effect of naloxone or pretreatment with morphine.

The purpose of the present study was firstly to determine whether morphine and (D-Ala2, NMe-Phe4, Gly-ol)-enkephalin (DAGO), a highly selective mu-agonist, increased intracellular free calcium of rat myocytes and secondly to determine whether opioid receptors were involved. Two series of experiments were performed. In the first, the effect of morphine and DAGO on intracellular free calcium (Cai) of cultured isolated myocytes was studied with a spectrophotometric method using fura2-AM as the fluorescent Ca2+ indicator. In the second, the effect of morphine on Cai of isolated ventricular myocytes from rats which had received chronic daily injection of morphine for two weeks or myocytes which had been incubated in a solution with morphine for 12 hr was studied. It was found that both morphine at 100-250 microM and DAGO at 23-75 microM increased Cai dose-dependently and that the effect was significantly antagonized by naloxone at a concentration of 50 microM, which itself did not cause any significant alteration in Cai. Pretreatment with morphine also abolished the morphine-induced increase in Cai of isolated myocytes. The results suggest that morphine increases Cai by directly activating the cardiac receptors (most likely micro-receptors) on the membrane of ventricular myocytes.

Cholera toxin enhances ischemia-induced arrhythmias in the isolated rat heart--involvement of a guanine nucleotide binding protein (Gs).

Cholera toxin (CTX) at a dose, which disturbed the intestinal functions, was administered into the rat via the tail vein. At 3 hr after injection, the heart was removed and perfused or subject to global ischemia in the Langendorff isolated heart preparation. Electrocardiogram (ECG) was recorded throughout the experiment. The myocardial cAMP content was measured in the intact non-ischemic heart, and in the isolated ischemic heart at 2.5, 5 and 10 min after ischemia. It was found that the incidence and severity of malignant ventricular arrhythmias including ventricular tachycardia (VT) and ventricular fibrillation (VF) was significantly increased during ischemia in the CTX treated group. The cAMP content was also significantly increased in the CTX treated group in both intact non-ischemic and ischemic hearts, indicating an activation of the guanine nucleotide regulatory protein (Gs). The results of the present study provide evidence that activation of Gs during ischemia may also contribute to the genesis of arrhythmia.

Study on bladder cancer susceptibility and genetic polymorphisms of XPC, XPG, and CYP in smokers and non-smokers.

AIM: To investigate the gene susceptibility of bladder cancer and potential relation with smoking. METHODS: An analysis of SNPs were conducted among DNA repair genes of XPC, XPG, XRCC1, and six members of metabolic enzyme gene CYP 450 via TaqMan Probe-based polymerase chain reaction. A total of 130 patients with bladder cancer and 304 healthy controls were involved. RESULTS: Polymorphisms of XPC gene was related to bladder cancer. It was also related to smoking status in bladder cancer patients, as well as to tumour stage, male gender and older age. The XPG gene polymorphism was also related to bladder cancer yet it was prevalent in female non-smokers. No association was acquired for XRCC1 gene. The combination of more than 2 polymorphisms in DNA repair genes was associated with bladder cancer. No association was obtained in any of the metabolic enzyme gene of CYP450 with either bladder cancer or smoking status. CONCLUSION: DNA repair genes XPC and XPG could be related to carcinogenesis and tumour progression of bladder cancer. Confirmation within larger population was warranted.

Primary salivary gland-type carcinomas of the nasopharynx: prognostic factors and outcome.

Primary salivary gland-type carcinomas of the nasopharynx (SNPC) are a rare malignancy with diverse clinical behaviour and different prognoses. Previous studies have reported on limited patient populations, and few long-term studies have outlined outcomes and prognostic factors. Controversy exists regarding the treatment policy for SNPC. The aim of this study was to define management approaches, therapeutic outcomes, and prognostic factors for SNPC. The medical records of 54 patients with SNPC at one institution between 1963 and 2006 were reviewed. Patient records were analysed for management approaches, outcomes, and prognostic factors. After a median follow-up of 61.3 (1.8-245.2) months, the 2-, and 5-year overall survival rates (OS), loco-regional failure free survival rates (LRFFS) and distant failure free survival rates (DFFS) were 84.6% and 61.3%, 74.4% and 55.4%, and 92.0% and 70.0%, respectively. Multivariate analyses indicated that lymph node metastases, date of treatment, and surgical treatment were independent factors for DFFS, whereas histological subtypes and distant metastases were independent factors affecting OS. The optimal treatment policy for patients with SNPC might be surgery plus radiotherapy.

Reentrant wetting transition on surfactant solution surfaces.

The wetting of polydimethylsiloxane oil drops on the surfaces of anionic surfactant sodium dodecylsulfate solutions is studied systematically by changing the bulk surfactant concentration. The wetting state changes from complete wetting to pseudopartial wetting at 0.3 cmc (critical micelle concentration) surfactant concentration and there is a reentrant transition back to complete wetting at 1.4 cmc. The measured free energy is consistent with the prediction of the wetting theory. The interaction potential minimum of the two surfaces of the oil film disappears at the reentrant point, which is speculated to be an effect of micelle formation in the solution.

Arrhythmogenic effect of forskolin in the isolated perfused rat heart: influence of nifedipine or reduction of external calcium [corrected].

1. This study investigated first the effects of forskolin on cardiac rhythm, and second the roles of calcium in cardiac arrhythmogenesis by cAMP. 2. Two series of experiments were performed. In the first series, forskolin was administered into the isolated perfused rat heart. In the second series, forskolin administration was preceded by administration of nifedipine, a calcium channel blocker, or infusion of a low concentration calcium solution. In both experiments, the myocardial cAMP level and electrocardiogram were determined. 3. It was found that forskolin increased cAMP level as well as inducing arrhythmia. Pretreatment with nifedipine or a reduction of external calcium, that either maintained or further enhanced the forskolin-induced increase in the cAMP level, abolished the forskolin-induced arrhythmia. 4. The results of the present study support the hypothesis that myocardial cAMP mediates cardiac arrhythmia, and provide evidence that calcium is essential in arrhythmia mediated by cAMP.

Increased polycyclic aromatic hydrocarbon toxicity following their photomodification in natural sunlight: impacts on the duckweed Lemna gibba L. G-3.

The authors previously demonstrated that simulated solar radiation (SSR), with a fluence rate of only 40 mumol m-2 sec-1, increased polycyclic aromatic hydrocarbon (PAH) toxicity to the duckweed Lemna gibba and that PAHs photomodified in SSR (generally oxygenation of the ring system) are more toxic than the parent compounds (Huang et al., Environ. Toxicol. Chem., 1993, 12, 1067-1077). It is not known, however, to what extent toxicity of PAHs can increase due to photomodification. Thus, natural sunlight, which has a high fluence rate (approximately 2000 mumol m-2 sec-1), was used to photomodify anthracene, benzo[a]pyrene, fluoranthene, phenanthrene, and pyrene. Toxicity was based on growth inhibition of L. gibba, measured as the rate of production of new leaves over an 8-day period. Initially, the toxicity of the PAHs applied in intact form was probed, with the compounds demonstrating greater toxicity in sunlight than in SSR. Next the PAHs were photomodified in sunlight prior to incubation with the plants. The half-lives of the PAHs in sunlight ranged from 12 min to 30 hr. Although most of the products of PAH photomodification are not yet identified, the degree that PAH toxicity increased following photomodification in sunlight could still be probed. The mixtures of photomodified chemicals that were derived from each PAH in sunlight were applied of L. gibba and growth inhibition under 100 mumol m-2 sec-1 of SSR was determined. The LC50s for the PAH photoproducts generated in sunlight were an order of magnitude lower than the LC50s for the PAHs applied in intact form.