Objective:To analyze the influence of clinicopathological features on the prognosis of anorectal malignant melanoma (AMM), and to establish a more accurate prognosis prediction model.Methods:From January 1, 2006 to December 31, 2018, at Fudan University Shanghai Cancer Center, the data of 89 patients diagnosed with AMM and underwent operation were retrospectively analyzed. The Cox proportional hazard regression model was used to analyze factors affecting the prognosis. Backward elimination was used to select variables, Nomogram prognosis prediction model was established and verified internally, and the consistency index was calculated.Results:Among 89 AMM patients, 65 (73.0%) were female, 78(87.6%) were <70 years old, and the most common tumor location was the rectum (48.3%, n=43), followed by the anal canal (31.5%, n=28) and the anorectal canal (20.2%, n=18). Thirty-eight (42.7%) patients directly received abdominal-perineal resection (APR), 37 patients (41.6%) received interferon-based immunotherapy, and 11 patients (12.4%) received both systemic chemotherapy and immunotherapy. The 3-year disease-specific survival (DSS) rate was 41.6%(37/89), and the 5-year DSS rate was 31.5%(28/89). The results of multivariate Cox analysis showed that age ≥70 years old and T2 stage were risk factors of the prognosis of AMM patients (hazard ratio ( HR)=11.29, 4.83; 95% confidence interval ( CI) 2.89 to 44.13, 1.66 to 14.11; both P<0.01), while neurovascular invasion, immunotherapy treatment, systemic chemotherapy combined with immunotherapy, APR after extensive local resection, directly APR and APR combined with inguinal lymphadenectomy were protective factors of the prognosis ( HR=0.09, 0.23, 0.10, 0.13, 0.26, 0.02; 95% CI 0.02 to 0.34, 0.10 to 0.57, 0.02 to 0.49, 0.03 to 0.52, 0.08 to 0.90, 0.00 to 0.27; all P<0.05). The Nomogram model was further established with age, gender, tumor location, T stage, distant metastasis, medication chemotherapy and surgical treatment. The results of the Nomogram model internal verification indicated that the accuracy of the model in predicting 1-year, 3-year and 5-year DSS was good, and the consistency index was 0.749, which was significantly higher than the consistency index of traditional TNM stage (0.607). Conclusions:Most AMM patients are <70 years old, and the majority of them are female. The common location of AMM is rectum, and many patients receive immunotherapy. Age ≥70 years old and T2 stage are risk factors affecting the prognosis of AMM patients. Neurovascalar invasion, immunotherapy based comprehensive treatment, APR after extensive local resection, directly APR and APR combined with inguinal lymphadenectomy are protective factors of the prognosis. Nomogram prognosis prediction model established based on the clinicopathological features and treatment of AMM patients has higher accuracy and clinical reference value than the traditional TNM stage system.

OBJECTIVE:To optimize the extraction technology for flavonoids in leaves and seeds of Hippophae rhamnoides. METHODS:Using the total extraction rate of 6 flavonoid aglycones(catechins,rutin,myricetin,quercetin,kaempferol,isorham-netin)as index,ethanol volume fraction,extraction time,extraction times,material-lipid ratio as investigation indexes,L9(34)or-thogonal test was designed to optimize the extraction technology of flavonoids in leaves and seeds of H. rhamnoides,and verifica-tion test was carried out. RESULTS:The optimum extraction technology for flavonoids in leaves of H. rhamnoides was ethanol vol-ume fraction of 70%,extracting for 3 times with material-lipid ratio of 1:16,and 2.0 h each time;and that of seeds was ethanol volume fraction of 50%,extracting for 3 times with material-lipid ratio of 1:24,and 1.5 h each time. In verification test,the total extraction rate of 6 flavonoid aglycones was 56.4 mg/g in the leaves (RSD=1.4%,n=3) and 15.4 mg/g in the seeds (RSD=3.4%,n=3). CONCLUSIONS:Optimized extraction technology is simple,stable,feasible,and can be used for extracting the fla-vonoids in leaves and seeds of H. rhamnoides.

An analytical method was developed for the determination of five carbohydrate impurities in amino acid drug substances by high performance liquid chromatography-evaporative light scattering detection (HPLC-ELSD). Sugar impurities in the amino acid sample were separated and enriched by cation exchange resin. A Lichropher NH2 column (4.6 mm × 250 mm, 5 μm) was used for chromatographic separation, and a gradient elution was performed using acetonitrile-water as mobile phase. The drift tube temperature was 40 oC, the gain value was 8, and nitrogen (350 kPa) was auxiliary gas. Method validation results showed that the limits of detection for fructose, glucose, sucrose, maltose and lactose were in the range of 20.8-75.0 mg/kg and that the limits of quantitation were in the range of 96.2-238.8 mg/kg. Good linear relationship (r ≥ 0.999) were in the linear range for the five sugars, and the recoveries ranged from 84.9%-107.8%. With easy operation, high sensitivity, good precision and reliable accuracy, the method can be used for analysis of residual sugar impurities in amino acid drug bulk drug.

To establish a rapid determination method of six flavonoids:catechin,rutin,myricetin,quercetin,kaempferol and isorhamnetin,from seabuckthorn leaves by RP-HPLC-DAD.The seabuckthorn leaves were first degreased by petroleum ether,extracted by ethanol,and determined by RP-HPLC-DAD.The six flavonoids were separated and eluted by a Shimadzu C18(150 mm ×2.1 mm,5 μm) column with methanol-water (0.1％ phos phoric acid) (60∶ 40) at a flow rate of 1.0 mL/min.The detection wavelength were as follow:catechin 208 nm,rutin 257 nm,myricetin 373 nm,quercetin 371 nm,kaempferol 367 nm,and isorhamnetin 371 nm,respectively.The injection volume was 20 μL.The contents of the six flavonoids were in the range of 0.47 to 30.00 μ,g/mL with good linearity.The validation of the method,including precision,stability and recovery rate,was acceptable.The established method can be used for fast determination of the content of six flavonoids in seabuckthorn leaves.

Objective To investigate the risk of atopic disease in infants with a atopic mothers. Methods The level of CCL22 and total IgE in the cord blood were measured using ELISA for 33 newborns with atopic mothers and for 44 newborns with non-atopic mothers. Correlation between the two factors was examined. Periodic follow-ups were conducted on the newborns to observe the risk of atopic diseases. Results The atopic group showed a higher level of CCL22 than that in non-atopic group, and the difference was statistically significant (Z=5.20, P=0.000). When 0.9 kU/L was taken as the threshold of an elevated IgE level in cord blood, the positive rates of the atopic group (11/33) was much higher than that of the non-atopic group (4/44) (χ2=7.07, P=0.008). Furthermore, the level of CCL22 and the level of IgE were significantly positively correlated (r=0.808, P=0.000; r=0.348, P=0.021) in the atopic group and the non-atopic group, respectively. During the 12 months of follow-up, the number of atopic diseases occurred in the infants in the atopic group (24/33) was much higher than that in the non-atopic group (10/44) (χ2=19.12, P<0.001).Significant correlation exists between levels CCL22 and total IgE in cord blood and infant atopic diseases (Z=5.36, P=0.000; Z=4.44, P=0.000). Conclusions At birth, the infants with an atopic mother are already in a sensitization state and have a tendency to develop potential atopic diseases. There is a correlation between the history of atopic diseases in the mothers and the elevated level of CCL22 in the cord blood of the newborns, and the probability of developing atopic diseases for the newborns is significantly higher when the level of CCL22 is elevated. The combined detection of CCL22 and IgE levels impact significantly on the prediction of the risk of atopic diseases clinically.

Objective: To analyze the influence of atmospheric particulate matters (PM_2.5 and PM₁₀) on low-birth-weight (LBW) infants at different periods of gestation. Methods: We conducted a systematic literature search for 2 471 articles related to particulate matter and LBW published from January 1st 2000 to January 1st 2016 using the PubMed, Cochrane Library, Web of Science, Science Direct, Chinese Web of Knowledge, Wanfang and Weipu, and the keywords were" air pollution" , "adverse birth outcomes" , "adverse pregnancy outcomes" , "low birth weight/LBW" . According to criteria, 27 literatures were selected and included. Metafor package of the R 3.1.1 Software was used to check the heterogeneity and merge the effect value of the selected literatures, and sensitivity analysis and publication bias were detected and adjusted. Results: A total of 2 471 studies selected form the databases, 27 enrolled in this analysis according to the inclusion and exclusion criteria. Each 10 μg/m³ increase in PM_2.5 was associated with combined OR values of 1st trimester, 2nd trimester, 3rd trimester and entire gestation at 1.02(95% CI: 0.87-1.19), 1.03 (95% CI: 0.91-1.16) , 1.07 (95%CI: 1.04-1.11) and 1.09 (95%CI: 1.04-1.15), respectively. And 10 μg/m³ increase in PM₁₀ was associated with combined OR values of 1st trimester, 2nd trimester, 3rd trimester and entire gestation at 1.66 (95%CI: 1.06-2.61), 1.58 (95%CI:1.28-1.95) , 1.38 (95%CI: 1.23-1.56) and 1.04 (95%CI: 0.99-1.09), respectively. After adjusting the bias of publication, each 10 μg/m³ increase in PM_2.5 was associated with the risk of low birth weight at 1.11 (95%CI: 1.02-1.21). Conclusion This meta analysis supports an adverse impact of maternal exposure to particulate air pollution on low birth weight, varying in effects by exposure period.

Carotid web is a rare risk factor of ischemic stroke.A total of 32 (0.54％) patients with carotid web were finally diagnosed in 5 943 patients who underwent carotid computerized tomography angiography (CTA) in two hospitals.Only one patient received carotid endarterectomy that pathological findings were fibrous tissue hyperplasia of vascular wall with mucinous degeneration.Stent implantation was administrated in two cases.Among 13 asymptomatic patients,the observational follow-up period was (20.9± 12.4) months without strokes.Carotid web is a rare aberration.Asymptomatic patients with carotid web are usually silent.Large sized cohort and long-term follow-up are further needed.

OBJECTIVE：To desig n and sy nthesize poly （γ-glutamic acid ）-ampelopsin（γ-PGA-AMP），and to characterize it and evaluate its anti-tumor activity in vitro . METHODS ：Synthetic product was produced through an esterification reaction between γ-PGA and ampelopsin. The structure of synthetic product was characterized by the UV spectrophotometry ，Fourier transform infrared（FT-IR）spectroscopy，1H-NMR spectra and the quantitative elemental analysis. The content of ampelopsin in synthetic product was determined by UV absorption spectrometry at 292 nm. Using 5-FU as positive control ，MTT assay was used to determine inhibitory effects of γ-PGA-AMP and ampelopsin on human breast cancer cell MCF- 7，human liver cancer cell HepG 2 and human lung cancer cell A 549. The IC 50 was calculated. RESULTS ：The results showed that the free 7-hydroxyl group of ampelopsin and the a-carboxyl group of γ-polyglutamic acid had been esterified to obtain γ-PGA-AMP；the yield of γ-PGA-AMP was 55.7％，and the content of ampelopsin was 32.3％. The inhibitory effect of γ-PGA-AMP and ampelopsin on MCF- 7，HepG2 and A 549 cells was obvious. IC 50 of γ-PGA-AMP（to 3 above tumor cells ）were 40.19，28.29 and 55.23 μg/mL，those of ampelopsin were 105.30，81.23，130.10 μg/mL，those of 5-FU were 24.72，87.98，30.99 μg/mL，respectively. CONCLUSIONS ：γ-PGA-AMP with anti-tumor effect in vitro is synthesized successfully ，and its anti-tumor effect is stronger than that of ampelopsin.

Objective Using time?series analyses to determine the association between ambient air pollution and stroke mortality in Jiang'an District of Wuhan, China from 2003 to 2010.Methods Data on daily stroke mortality for the period 2003 January 1 to 2010 December 31 was obtained from Jiang'an District Center for Disease Control and Prevention, Wuhan and data on relevant air pollution and meteorological factors from the local municipal environmental monitoring center and meteorology bureau of Wuhan, respectively. Application of a time-series analysis in generalized additive model was applied to evaluate the association between air pollution and stroke mortality. Results Annual average concentrations of PM10, SO2 and NO2 during the study period were (115.0 ± 60.0), (50.2 ± 33.7), and (57.6 ± 25.3)μg/m3, respectively. The total stroke death was 9 204, including 4 495 women, and 7 628 people aged over 65?years old. In single?pollutant model, a 10μg/m3 increase in previous day (lag 1 d) ambient pollutants was associated with 0.67%(95%CI:0.25%-1.10%) excess risk in stroke mortality for PM10, 0.87%(95%CI:0.13%-1.63%) excess risk for SO2 and 2.07% (95%CI: 1.08%-3.07%) excess risk for NO2, respectively. When co-pollutants were involved into the models, only NO2 remained strongly associated with stroke mortality(β=2.07,95%CI:1.08-3.07, P<0.001). A 10μg/m3 increase of NO2 in lag 1 d was associated with 1.77%(95%CI:0.54%-3.01%), 2.27%(95%CI:0.98%-3.57%) and 2.00%(95%CI:0.59%-3.43%) excess risk in stroke mortality, respectively, after adjusting for PM10, SO2, both PM10 and SO2. Age?specific and gender?specific analyses showed that the association between ambient air pollution and stroke mortality was stronger in the elderly (≥65 years old) people and women. A 10μg/m3 increase of PM10, SO2 and NO2 in lag 1 d was associated with excess stroke mortality of 0.97%(95%CI:0.37%-1.57%), 1.73%(95%CI:0.69%-2.78%) and 2.98% (95%CI:1.59%-4.39%) for women, respectively and 0.94%(95%CI:0.47%-1.42%), 1.06%(95%CI: 0.23%-1.90%) and 2.50%(95%CI:1.40%-3.62%) for the elderly people (>65 years old), respectively. Conclusion PM10 and gaseous pollutants (SO2, NO2) were significant risk factors for acute stroke death, and people aged over 65?years old and women were more susceptible to the effect of ambient pollutants on stroke mortality.

Objective Using time?series analyses to determine the association between ambient air pollution and stroke mortality in Jiang'an District of Wuhan, China from 2003 to 2010.Methods Data on daily stroke mortality for the period 2003 January 1 to 2010 December 31 was obtained from Jiang'an District Center for Disease Control and Prevention, Wuhan and data on relevant air pollution and meteorological factors from the local municipal environmental monitoring center and meteorology bureau of Wuhan, respectively. Application of a time-series analysis in generalized additive model was applied to evaluate the association between air pollution and stroke mortality. Results Annual average concentrations of PM10, SO2 and NO2 during the study period were (115.0 ± 60.0), (50.2 ± 33.7), and (57.6 ± 25.3)μg/m3, respectively. The total stroke death was 9 204, including 4 495 women, and 7 628 people aged over 65?years old. In single?pollutant model, a 10μg/m3 increase in previous day (lag 1 d) ambient pollutants was associated with 0.67%(95%CI:0.25%-1.10%) excess risk in stroke mortality for PM10, 0.87%(95%CI:0.13%-1.63%) excess risk for SO2 and 2.07% (95%CI: 1.08%-3.07%) excess risk for NO2, respectively. When co-pollutants were involved into the models, only NO2 remained strongly associated with stroke mortality(β=2.07,95%CI:1.08-3.07, P<0.001). A 10μg/m3 increase of NO2 in lag 1 d was associated with 1.77%(95%CI:0.54%-3.01%), 2.27%(95%CI:0.98%-3.57%) and 2.00%(95%CI:0.59%-3.43%) excess risk in stroke mortality, respectively, after adjusting for PM10, SO2, both PM10 and SO2. Age?specific and gender?specific analyses showed that the association between ambient air pollution and stroke mortality was stronger in the elderly (≥65 years old) people and women. A 10μg/m3 increase of PM10, SO2 and NO2 in lag 1 d was associated with excess stroke mortality of 0.97%(95%CI:0.37%-1.57%), 1.73%(95%CI:0.69%-2.78%) and 2.98% (95%CI:1.59%-4.39%) for women, respectively and 0.94%(95%CI:0.47%-1.42%), 1.06%(95%CI: 0.23%-1.90%) and 2.50%(95%CI:1.40%-3.62%) for the elderly people (>65 years old), respectively. Conclusion PM10 and gaseous pollutants (SO2, NO2) were significant risk factors for acute stroke death, and people aged over 65?years old and women were more susceptible to the effect of ambient pollutants on stroke mortality.