chronic cervicitis(0%),(P=0.000).The positive rates of EPMMPRIN overexpression in metastatic lymph nodes was 54.5%(12/22),no difference was found from corresponding primary tumor(72.7%,P=0.210).But EMMPRIN overexpression in primary tumor was related to lymph node metastasis(P=0.026),no relationship was found between EMMPRIN expression and other clinical-pathological parameters.Univariate analyses revealed that EMMPRIN expression did not correlate to tumor-specific survival.In contrast,lymph vascular space invasion,deep stromal invasion and lymph node metastasis were significantlyassociated with poor prognosis.In multivariate analysis,lymph-node metastasis was the independent prognostic factor for tumor-specific survival(P=0.006;HR=0.038;95% confidence interval,0.0190.763).Conclusion:EMMPRIN overexpression may play an important role in progression of human cervical cancer,and in the development of cervical cancer from CIN.

AIM　To study the synthesis of zinc chlorin e4 (1), its experimental antigastrelcosis activity as well as the protection against acute liver injuries. METHODS　Chlorin e6 (3) was prepared through acidic and alkaline oxidative degradation using silkworm excrement crude chlorophyll extracts as starting material. Compound 1 was synthesized via Zn(OAc)2 complex action with Chlorin e4 (2) which was prepared by refluxing 3 in pyridine. Gastric ulcers were induced by abdominal injection of 0.2% indomethacin at 20 mg.kg-1 in rats. The ulcer indexes and ulcer numbers in gastric mucosa were determined. Acute liver injuries were induced by abdominal injection of 0.3% thioacetamide (TAA) or 0.3% CCl4 at 20 mg.kg-1 in mice, and activities of SGPT in mice were determined. RESULTS　Compound 1 is previously unknown. Compared with control group, abdominal administration of 1 at 100 mg.kg-1 reduced significantly the gastric ulcer index (P<0.001) and the number of ulcer (P<0.001) induced by indomethacin in rats. Abdominal administration of 1 at 100 mg.kg-1×3 exhibited marked inhibitory effects on elevated activities of SGPT induced by TAA (P<0.02) or CCl4 (P<0.01) in mice. CONCLUSION　These results show that 1 has significant protective effect against indomethacin-induced gastric lesion in rats and TAA or CCl4 induced acute liver injuries in mice. It is suggested that 1 may be a promising new drug candidate for antigastrelcosis and liver injury protection.

Objective To develop a small-diameter tissue-engineered blood vessels which possesses normal blood vessels physiological structure, good biocompatibility, and mechanical properties. And it was evaluated by mechanical and biological of national standard of medi-cal transfusion material. Methods The bio-derived material were regarded as the ground substance, and it was evaluated by mechanical and biological of national standard after composite modification. Results The axial and radial tensile stress of the blood vessel was 23. 14 N and 36. 79 N respectively, and it was greater than the standard 7. 5N. The tensile rate of the axial and radial was 95. 19% and 80. 24% respec-tively, which were higher than the standard value 20%. The suture strength of the blood vessel was 13. 71 N, which was conform to the me-chanical requirement. Mainly used blood vessels or its extracts to detect the pH of the blood vessels is in the scope of control deionized water pH (7. 5 ± 1. 5);the hemolysis rate was 1. 3972% which was less than 5%;the whole blood coagulation time was 50% longer than the con-trol level, and there was no stimulation after intradermal injection. Conclusion With bio-derived material as the ground substance and com-positely modified, this kind od blood vessels is conform to the mechanical and biological of national standard, and it has the potential of clini-cal application which could play an important role in the replacement therapy of small-diameter vascular xenografts.

Objective To evaluate the endoscopic and pathologic characteristics and etiological ex-amination of viral esophagitis. Methods The data of 16 patients with viral esophagitis, including endoscop-ic, pathological and immunohistochemical findings were retrospectively studied. Results Endoscopic find-ings of viral esophagitis were characterized by single or multiple round and oval ulcers, located at the upper and middle esophagus. The surface of the ulcer was clean, and the boundary was distinct. Pathologic findings included degeneration and necrosis in squamons epithelium, accompanied by ulcer, infiltration of neutrophils and lymphocytes, hyperplasia of capillaries and basal cells and formation of granulation tissues, Immunocyto-chemical examination showed HSV-1 was positive in biopses, while CMV, EBV, HHV8 were negetive. Con-dusion Viral esophagtitis exhibited distinctive endosoopic and pathological features, and etiology can be confirmed by immunohistochemical examinations.

OBJECTIVE:To investigate the inhibitory effect of Baixuan xiatare tablet on the model mouse with allergic contact dermatitis (ACD). METHODS:60 BALB/c mice were equally randomized into normal control (isometric solvent) group,model (isometric solvent)group,ebastine(positive control,0.003 g/kg)group and the groups of high,middle and low doses of Baixuan xiatare tablet(2.0,1.0 and 0.5 g/kg). The mice were given drugs,ig,once daily for 14 consecutive days. 0.5% 2,4-dinitrofluoro-benzene(DNFB)acetone olive oil solution was applied,for sensitization,on the prepared mouse’s skins one and two days before administration,and 0.2% DNFB acetone olive oil solution on their left ears 16 days thereafter to establish mouse models of ACD. At 48 h after successful establishment of the models,the thickness of the mouse’s left ear margin was measured and the difference value and swelling degree were calculated;flow cytometer was used to determine the levels of T lymphocyte subsets CD4+ and CD8+ in mouse blood and calculate the ratio of CD4+ to CD8+;the levels of interleukin 4(IL-4)and IL-6 in mouse serum were de-termined. RESULTS:Compared with normal control group,those in the model group had higher difference value of ear margin and swelling degree,lower level of CD4+ in blood and ratio of CD4+ to CD8+,and higher content of IL-6 in serum. There was statisti-cally difference (P<0.01). Compared with model group,those in the groups of high,middle and low doses of Baixuan xiatare tablet had lower degree of left ear swelling and higher level of CD4+ in blood;those in the groups of high and middle doses thereof had lower difference value of left ear margin and level of IL-6 in serum;and those in the group of high dose thereof had higher lev-el of CD8+ in blood. There was statistically significance(P<0.01 or P<0.05). CONCLUSIONS:Baixuan xiatare tablet has inhibi-tory effect to some degree on the mouse model with ACD by a mechanism which may be related to the balance of subsets CD4+and CD8+in blood and the reduction of IL-6 in serum.

Objective To determine the effectiveness and safety of stereotactic body radiotherapy (SBRT)-CyberKnife for oligometastatic prostate cancer.Methods From May 2012 to February 2017,31 patients treated by CyberKnife were retrospectively reviewed,with a median age of 67 years(range 52 to 83 years),including 50 oligometastatic and 2 primary prostate cancer patients.The median PSA level was 8.4 ng/ml(range 0 to 300.0 ng/ml) and PSA test was performed every month.PSA progression-free survival (PSA-PFS),time to initiation of androgen deprivation therapy (ADT) and local control rate (LCR) were measured as the main outcomes.Results SBRT was well tolerated and were performed as planned in all patients.No SBRT related acute or late toxicities were observed.No bone fracture was observed in patients treated by bony targeted radiotherapy.The median follow-up after SBRT was 20.7.months (range 1.2-58.3 months).The median PSA-PFS was 5.3 months (range 0-58.3 months).1-year,2-year,and 4-year PSA-PFS was 52.0％,36.7％ and 36.7％ respe ctively.PSA level decrease was observed in 21 oligometastatic prostate cancer patients after SBRT,with median PSA-PFS of 12.3 months (range 1.2-58.3 months).PSA level increase was observed in 29 oligometastatic prostate cancer patients after SBRT.Six local recurrence were observed resulting in an actuarial 1-year,2-year and 3-year LCR of 90.4％,86.9％ and 82.6％,respectively.Twelve patients treated without ADT after SBRT,with median follow-up of 8.6 months (range 2.9-58.3 months) in this subgroup.Seven patients were added ADT after SBRT,with the median time from SBRT to initiation of ADT of 13.3 months (range 3.0-24.0 months) in this subgroup.Twelve patients were treated with ADT continuously after SBRT.Conclusions CyberKnife seems to be a safe and effective treatment with tolerated adverse events and good local control for patients with oligometastatic prostate cancer.

Objective To assess the clinical value of endoscopic uhrasonography(EUS)combined with the mini-probe endoscopic uhrasonography(MPUS)in determing tumor invasion depth and lymph node metastases of early superficial esophageal cancer.Methods One hundred and twenty-four superficial esophageal cancer lesions of 121 patients were staged by EUS combined with MPUS,and the results were finally compared with pathological findings of surgical specimens or samples obtained by mucosal resection.Results The diagnostic accuracy of EUS in T staging of superficial esophageal cancer was 82.3%(102/124).The total ratio of lymph node metastases was 5.0%(6/121),with no node metastases in carcinoma in situ,1.3%(1/28)in mucosal carcinoma,11.6%(5/43)in submucosal carcinoma.Conclusion EUS combined with MPUS is accurate in staging of the superficial carcinoma,which can help the choice of therapeutic strategies.

Objective To determine the effectiveness and safety of patients treated with stereotactic body radiotherapy ( SBRT ) - CyberKnife for small hepatocellular carcinoma. Methods A prospective analysis of treatment details and outcomes for 33 patients with small hepatocellular carcinoma treated by CyberKnife at CyberKnife center of Shanghai Changhai Hospital from June 2014 to December 2016 was presented. Patients were followed every 3 months. WHO modified response evaluation criteria in solid Tumors( mRECIST) was used to evaluate efficacy, Common Terminology Criteria for Adverse Events Version 4. 0(CTCAE 4. 0) to evaluate treatment response, Kaplan-Meier method to calculate survival rate and local control rate and plot survival curves. Results There were 33 patients, 33 targets included in the study at the date of the last follow-up. 18 lesions (54. 5%) showed complete remission response, 7 lesions (21. 2%) showed partial remission response, 5 lesions (15. 2%) showed stable, and 3 lesions (9. 1%) progressed. Response rate was 75. 8%, and disease control rate was 90. 9%. 1- and 2-year local control rate was 100% and 83. 6%, respectively. The median disease progression free survival ( DPFS) was 15. 0 months. Non irradiated liver volume more than 100 ml, prior AFP less than 100 ng/ml, post-treatment CTCAE less than grade 2 could improve overall survival ( OS ) . V5 was a factor in grades 2 -4 hepatic toxicity ( P=0. 015 ) . All patients tolerated the radiosurgery, with grade 1 and grade 2 fatigue, and the gastrointestinal reactions and liver injury was the main side effect. 1 patient with grade 3 liver damage relieved at 6 months after treatment and 1 patient with grade 4 liver damage cured at 12 months after treatment. No grade 5 toxicity was encountered. Conclusions CyberKnife seems to be a safe and effective treatment measure with tolerated adverse reaction and good local control rate for patients with small hepatocellular carcinoma.

Objective:To investigate the effects of circ_000543 derived from hypoxic exosomes on proliferation and invasion of breast cancer (BC) cells.Methods:Bioinformatic website was used to predict the abnormal expression of circ_000543 in BC tissue and the transcription factor that might regulate circ_000543. Double luciferase report experiment and ChIP assay were used to confirm the regulation relationship between YY1 and circ_000543. Exosomes were separated from normal BC cells and BC cells under hypoxic condition, and qRT-PCR was adopted to detect the expression of circ_000543 in exosomes. The expression of circ_000543 and YY1 in exosomes was intervened and the exosomes were cocultured with BC cells under normoxia. CCK8 and Transwell assay was used to detect the proliferation and invasive ability individually.Results:qRT-PCR experiment found that, compared with MCF-10A cells (1±0.11) and exosomes isolated from normoxic cells (1±0.10), circ_000543 expression was up-regulated in BC cells (1.59±0.13) and exosomes derived from cells under hypoxic condition (1.63±0.12) ( t=6.001, P=0.004; t=6.986, P=0.002). Exosomes derived from cells under hypoxic condition promoted proliferation and invasion of BC cells under normoxia. Inhibition of circ_000543 partially offset the effects of exosomes. YY1 induced the expression of circ_000543 in BC cells as a transcription factor. The expression of circ_000543 was inhibited when YY1 expression was down-regulated; at the same time, down-regulation of YY1 inhibited the effects of exosomes on proliferation and invasion of BC cells. Conclusion:The transcription factor YY1 promoted proliferation and invasion of BC cells by inducing hypoxic breast cancer-derived exosomal circ_000543.

Objective:To investigate the effect of methyltransferase like 14 (METTL14) on the proliferation and invasion of breast cancer (BC) cells by regulating cyclin L2 (Cyclin L2, CCNL2) through m6A modification.Methods:Cancer tissues and paracancerous tissues of BC patients in Yantaishan hospital were collected from Aug. 2018 to Feb. 2020. The expression levels of m6A, METTL14 and CCNL2 in tissues were detected by high performance liquid chromatography/mass spectrometry (HPLC/MS) and qRT-PCR. Dual-luciferase reporter assay, qRT-PCR, and western blot were used to verify the regulatory relationship between METTL14 and CCNL2. RIP experiments verified the regulatory relationship between YTH domain-containing family protein (YTHDF2) and CCNL2. Cell viability was detected by MTT method, and cell invasion ability was detected by Transwell.Results:Compared with normal cells (0.24±0.02) and tissues (0.18±0.02) , BC cells MCF-10A (0.47±0.03, t=11.05, P<0.001) and HS-578T (0.41±0.03, t=8.17, P=0.001) and BC tissues (0.39±0.02, t=12.86, P<0.001) m6A level increased. Compared with normal tissues (1.00±0.26) (0.84±0.07) , METTL14 mRNA (1.57±0.28, t=13.50, P<0.001) and protein levels (1.66±0.11, t=10.89, P<0.001) in BC tissues were significantly increased high. Compared with the control group (100.00±10.11) (1.00±0.12) , the BC cell invasion ability (54.15±6.21, t=6.69, P=0.003) and activity (0.64±0.06, t=4.65, P=0.010) were weakened. Compared with the control group (100±11.05) (1±0.13) , the BC cell invasion ability (175.31±13.45, t=7.49, P=0.002) and activity (2.16±0.16, t=9.75, P=0.002) in the METTL14 overexpression group were enhanced, and the effects of METTL14 on cell invasion (137.41±12.64, t=3.56, P=0.024) and activity (1.64±0.15, t=5.59, P=0.005) were partially reversed after m6A inhibitor treatment change. Compared with normal tissues, CCNL2 expression was down-regulated in BC tissues, and the interaction between CCNL2 and METTL14 was confirmed. Compared with the control group (1.00±0.1) (0.64±0.05) , knockdown of METTL14 could make CCNL2 mRNA (1.67±0.05) . 0.13, t=7.08, P=0.002) and protein (1.09±0.09, t=7.57, P=0.002) were up-regulated. METTL14 knockout enhanced the stability of CCNL2 mRNA through a YTHDF2-dependent pathway, compared with sh-METTL14 group (50.47±5.16) (0.52±0.05) , BC cell invasion ability of sh-METTL14+sh-CCNL2 group (71.69±6.41, t=4.47, P=0.011) and activity (0.64±0.05, t=2.94, P=0.042) were improved. Conclusion:METTL14 inhibits the expression of CCNL2 through m6A modification to enhance the invasion and activity of BC cells.