Objective:To evaluate the efficacy and safety of hypomethylating agents (HMA) in patients with myelodysplastic syndromes (MDS) .Methods:A total of 409 MDS patients from 45 hospitals in Zhejiang province who received at least four consecutive cycles of HMA monotherapy as initial therapy were enrolled to evaluate the efficacy and safety of HMA. Mann-Whitney U or Chi-square tests were used to compare the differences in the clinical data. Logistic regression and Cox regression were used to analyze the factors affecting efficacy and survival. Kaplan-Meier was used for survival analysis. Results:Patients received HMA treatment for a median of 6 cycles (range, 4-25 cycles) . The complete remission (CR) rate was 33.98% and the overall response rate (ORR) was 77.02%. Multivariate analysis revealed that complex karyotype ( P=0.02, OR=0.39, 95% CI 0.18-0.84) was an independent favorable factor for CR rate. TP53 mutation ( P=0.02, OR=0.22, 95% CI 0.06-0.77) was a predictive factor for a higher ORR. The median OS for the HMA-treated patients was 25.67 (95% CI 21.14-30.19) months. HMA response ( P=0.036, HR=0.47, 95% CI 0.23-0.95) was an independent favorable prognostic factor, whereas complex karyotype ( P=0.024, HR=2.14, 95% CI 1.10-4.15) , leukemia transformation ( P<0.001, HR=2.839, 95% CI 1.64-4.92) , and TP53 mutation ( P=0.012, HR=2.19, 95% CI 1.19-4.07) were independent adverse prognostic factors. There was no significant difference in efficacy and survival between the reduced and standard doses of HMA. The CR rate and ORR of MDS patients treated with decitabine and azacitidine were not significantly different. The median OS of patients treated with decitabine was longer compared with that of patients treated with azacitidine (29.53 months vs 20.17 months, P=0.007) . The incidence of bone marrow suppression and pneumonia in the decitabine group was higher compared with that in the azacitidine group. Conclusion:Continuous and regular use of appropriate doses of hypomethylating agents may benefit MDS patients to the greatest extent if it is tolerated.

Cysteine protease inhibitor 1 (CST1) is a member of type 2 Cystatins superfamily, plays a key role in targeted regulation. CST1 is highly expressed in gastric cancer, promotes tumor cell migration and invasion by activating the epithelial-mesenchymal transformation pathway and Wnt pathway, and regulates tumor growth and progression in combination with the corresponding target genes of homeobox C10 and glutathione peroxidase 4. A deeper understanding of the role and function of CST1 in gastric cancer will help to further develop potential therapeutic targets and diagnostic and prognostic markers for gastric cancer.

Objective:To explore the safety, feasibility and clinical value of the "posterior colon approach, uncinate process first" of total laparoscopic pancreaticoduodenectomy in low volume hospitals.Methods:The clinical data of 3 patients who underwent complete laparoscopic pancreaticoduodenectomy were analyzed from January 2020 to August 2020.Results:All the 3 patients successfully underwent total laparoscopic pancreaticoduodenectomy. For the 3 patients, the operative time was 430, 385 and 425 min, and the blood loss was 550, 420 and 400 ml. After the operation, no pancreatic fistula, bile leakage, intestinal fistula and astric emptying disorder were found in the patients. The exhaust time of the 3 patients was 4, 5 and 5 days after the operation, respectively. On the 6th day after the operation, the gastric tube was removed. The extraction time of the abdominal drainage tube of the 3 patients was the 7th, 7th and the 9th day, and the postoperative hospital stay was 18, 15 and 16 days, respectively. Postoperative pathological diagnosis results showed that the 3 patients included 1 case of pancreatic head high-moderately differentiated ductal adenocarcinoma, 1 case of duodenal ampullary high-moderately differentiated adenocarcinoma, and 1 case of duodenal papillary well-differentiated adenocarcinoma.Conclusions:"Posterior approach of uncinate process" is safe and feasible in laparoscopic pancreaticoduodenectomy. It can be popularized in low volume hospitals.

Objective To investigate the clinical and prognostic significance of ABO promotor methylation level in adult patients with leukemia and myelodydysplastic syndrome(MDS). Methods ABO promoter methylation level of 182 malignant hematological disease patients and 68 normal controls were detected by bisulfite sequencing PCR. Then clinical features and outcome were compared between hypermethylation group and hypomethylation group. Results The median methylation rate of ABO promoter in newly diagnosed acute myeloid leukemia (AML) and acute lymphocytic leukemia (ALL) were 46.98％ and 11.01％ respectively, which were both higher than that in controls (2.30％, P<0.05). The methylation rates in remission AML and ALL were 1.58％and 2.30％respectively, which were comparable with that in normal group (P>0.05). As to relapse AML and ALL, methylation rates were 41.26％ and 17.50％respectively, also significantly higher than that in controls (P<0.05).In patients with chronic myeloid leukemia (CML) chronic phase, the median methylation rate was 1.00％, which was similar to normal group. But a CML patient who transformed to ALL hadextremely high methylation rate 92.56％. The median methylation rate in patients with MDS significantly elevated as 5.81％ compared with that in controls (P<0.05). The median overall survival (OS) of ALL and AML (non-M3) patients with hypermethylation were 12.5 months and 15.3 months, which were significantly shorter than those with hypomethylation (24.0 months and 20.0 months) (P<0.05). The median disease-free survival (DFS) of ALL and AML (non-M3) patients with hypermethylation were 9.9 months and 12.0 months, which were significantly shorter than those with hypomethylation (22.3 months and 18.5 months), (P<0.05). Multivariable analysis suggested that ABO promoter methylation level was an independent predictive factor of OS and DFS in ALL and AML (non-M3) patients. Conclusion ABO promoter hypermethylation is closely related to genesis, development and prognosis of leukemia and MDS. Hypermethylationis related to a clinical poor prognosis compare with hypomethylation.

PURPOSE: c-Met and its ligand, hepatocyte growth factor (HGF), play a critical role in oncogenesis and metastatic progression. The aim of this study was to identify inhibited enzymogram and to test the antitumor activity of SIM-89 (a c-Met receptor tyrosine kinase inhibitor) in non-small cell lung cancer. MATERIALS AND METHODS: Z′-LYTE kinase assay was employed to screen the kinase enzymogram, and mechanism of action (MOA) analysis was used to identify the inhibited kinases. Cell proliferation was then analyzed by CCK8 assay, and cell migration was determined by transwell assay. The gene expression and the phosphorylation of c-Met were examined by realtime-PCR and western blotting, respectively. Finally, the secretion of HGF was detected by ELISA assay. RESULTS: c-Met, activated protein kinase (AMPK), and tyrosine kinase A (TRKA) were inhibited by SIM-89 with the IC₅₀ values of 297 nmol/L, 1.31 µmol/L, and 150.2 nmol/L, respectively. SIM-89 exerted adenosine triphosphate (ATP) competitive inhibition on c-Met. Moreover, the expressions of STAT1, JAK1, and c-Met in H460 cells were decreased by SIM-89 treatment, and c-Met phosphorylation was suppressed in A549, H441, H1299, and B16F10 cells by the treatment. In addition, SIM-89 treatment significantly decreased the level of HGF, which accounted for the activation of c-Met receptor tyrosine kinase. Finally, we showed cell proliferation inhibition and cell migration suppression in H460 and H1299 cells after SIM-89 treatment. CONCLUSION: In conclusion, SIM-89 inhibits tumor cell proliferation, migration and HGF autocrine, suggesting it's potential antitumor activity.
Adenosine Triphosphate ; Blotting, Western ; Carcinogenesis ; Carcinoma, Non-Small-Cell Lung* ; Cell Movement ; Cell Proliferation ; Enzyme-Linked Immunosorbent Assay ; Gene Expression ; Hepatocyte Growth Factor ; Lung Neoplasms ; Phosphorylation ; Phosphotransferases ; Protein Kinases ; Protein-Tyrosine Kinases

Objective To understand the current situation of scientific research integrity level of medical graduate students,the development of integrity education in their universities,to put forward corresponding suggestions for improvement.Methods From December 2015 to March 2016,128 postgraduates are selected as the participants of the survey by randomized method (123 responded).We conducted a questionnaire survey in four famous medical universities in Beijing,descriptive analytical method was adopted to analyze survey findings.The contents of survey included the status of academic integrity of the current medical students,education of academic integrity in Medical Universities,awareness of scientific integrity and acquisition channel of relevant knowledge.Results According to the survey,the awareness rate of research integrity is not high,scientific misconduct has occurred consciously or unconsciously.By analyzing the access and demands to knowledge of research integrity,we find that related seminars or lecture is the best channel to acquire academic research integrity knowledge,accounting for 61.48％.Followed by the curriculum of academic ethics and compliance aspects was the network information or communication with classmates,which accounts for 39.34％.The data also show that 95.90％ of respondents thought it is necessary for medical graduate students to accept academic ethics and norms of education,68.03％ of the respondents realized that cultivating students' awareness of scientific integrity in the process of scientific research gradually has great guiding significance for mentors and counselors.Conclusions The survey suggests that the education of scientific integrity in our country is very inadequate,the knowledge on good scientific integrity was fragmented.At present,most of the medical universities have not yet set up scientific integrity course,and access to the knowledge of integrity is limited for students.The scientific integrity education has become an extremely urgent issue for cultivating the sense of integrity in scientific research for researchers as soon as possible.

OBJECTIVETo describe the distribution of zinc (Zn) and copper (Cu) in urine samples of generalpopulation in eight provinces of China, to analyze their characteristics of distribution between different region, gender and age-cohorts, and to provide the baseline of themetabolites in the general population.

METHODSFrom 2009 to 2010, 18 120 subjects from the general population aged from 6 to 60 years old were recruited from 24 areas among 8 provinces of China mainland by random sampling. The environmental and physical condition characteristics were collected from questionnaires, and urine samples were collected at the mean time. The levels of Zn and Cu in urine were measured using ICP-MS. Data were analyzed by statistical methods to compare the distribution characteristics of Zn and Cu among populations with different ages and genders.

RESULTSTotally, the median of Cu and Zn in urine were 9.28 and 115.47 µg/L respectively; and the inter-quartile range of Cu and Zn were 2.66-16.09 and 35.32-265.15 µg/L respectively. The median of Cu in male and female were 9.90 and 8.60 µg/L (Z=-5.63, P<0.001), and Zn in male and female were 140.44 and 95.27 µg/L (Z=-14.79, P<0.001). The median of Cu among the groups aged 6-12, 13-16, 17-20, 21-30, 31-45 and 46-60 years old were 9.30, 10.14, 9.67, 9.33, 8.38 and 8.74 µg/L (χ2=70.94, P<0.001), respectively, and the median of Zn 130.83, 132.07, 139.34, 109.3, 78.74 and 109.51 µg/L ((χ2=146.00, P<0.001), respectively.There was statistically significant differences in urinary Cu and Zn levels between male and female, and among the different age groups.

CONCLUSIONThe Cu and Zn levels and distribution in urine among general population between 2009 and 2010 in China were reported in this article. These basic data in China will provide scientific and reliable reference for further scientific research.

Adolescent ; Adult ; Age Factors ; Child ; China ; Copper ; urine ; Environment ; Female ; Humans ; Male ; Middle Aged ; Sex Factors ; Surveys and Questionnaires ; Zinc ; urine

OBJECTIVETo evaluated the manganese (Mn), cobalt (Co) and molybdenum (Mo) levels in blood and urine among general population in China, and thereby to analyze their prevalent features.

METHODSFrom 2009 to 2010, a total of 18 120 subjects of general population aged 6-60 years were recruited from 24 districts in 8 provinces in eastern, central and western China mainland, by cluster random sampling method. The information about their living environment and health status were collected by questionnaire, and their blood and urine samples were also collected.Inductive coupled plasma mass spectrometry (ICP-MS) was applied to test the Mn, Co and Mo levels of blood and urine samples, and the Mn, Co, Mo distribution in blood and urine among groups of population in different ages and genders were then analyzed.

RESULTSAmong general population in China, the geometric mean (GM) of Mn concentration in blood was 8.98 µg/L. The Mn concentration in blood among males and females were separately 8.14 µg/L and 9.88 µg/L (Z = -18.84, P < 0.01). The GM of Mn concentration in urine was 0.63 µg/L. The Mn concentration in urine among males and females were separately 0.62 µg/L and 0.63 µg/L (Z = -0.67, P > 0.05). The geometric mean (GM) of Co concentration in blood was 0.194 µg/L. The Co concentration in blood among males and females were separately 0.166 µg/L and 0.225 µg/L (Z = -23.04, P < 0.01). The GM of Co concentration in urine was 0.282 µg/L. The Co concentration in urine among males and females were separately 0.260 µg/L and 0.307 µg/L (Z = -7.35, P < 0.01). The GM of Mo concentration in blood was 0.25 µg/L. The Mo concentration in blood among male and female group were separately 0.27 µg/L and 0.23 µg/L (Z = -5.03, P < 0.01). The GM of Mo concentration in urine was 27.7 µg/L. The Mo concentration in urine among males and females were 29.8 µg/L and 25.6 µg/L (Z = -6.31, P < 0.01), respectively.

CONCLUSIONThe Mn, Co and Mo levels in blood and urine varied by gender and area among general population in China, the study provided basic data evidence for the following Mn, Co and Mo biological monitoring studies in near future.

Adolescent ; Adult ; Child ; China ; epidemiology ; Cobalt ; Environmental Exposure ; Environmental Monitoring ; Female ; Humans ; Male ; Manganese ; Middle Aged ; Molybdenum

OBJECTIVETo investigate the level of zinc (Zn) and copper (Cu) in whole blood among general population from 8 provinces in China, and to analyze the characteristics of distribution among different regions.

METHODSThis cross-sectional study was performed in 8 provinces from eastern, middle and western China between 2009 and 2010, including 13 110 subjects from 24 regions, and the blood and urine samples were collected. The ICP-MS was applied to test the content of ICP-MS in blood samples, and the results were used to analyze the characteristics of contents and distributions of Zn and Cu among population from different ages, genders and regions groups.

RESULTSTotally, the mean (95%CI) contents of Cu and Zn in blood were 795 (791-799)µg/L and 3 996(3 976-4 015) µg/L, respectively. The characteristics of distribution of Cu content were as followed, the content of males were lower than it of females (male:767 µg/L; female: 822 µg/L, t = -13.302, P < 0.01). The contents of blood Cu in groups of people aging 6-12, 13-16, 17-20, 21-30, 31-45 and 46-60 years old were separately 860(853-868), 758(748-769), 734(728-734), 782(774-790), 811(795-827) and 820(815-826) µg/L. The differences showed statistical significance (F = 78.77, P < 0.01). The blood Cu content of people in eastern China (800µg/L) were also significantly higher than it in middle (774 µg/L)and western China (782 µg/L) (F = 10.94, P < 0.01). Distribution of blood Zn content showed characteristics as follows: the Zn content was higher in males than in females (male 4 085 µg/L and female 3 908 µg/L, t = 8.78, P < 0.01). The contents of blood Zn in groups of people aging 6-12, 13-16, 17-20, 21-30, 31-45 and 46-60 years old were separately 3 306 (3 261-3 350), 3 888 (3 839-3 937), 3 948 (3 902-3 994), 4 272(4 228-4 315), 4 231(4 180-4 281) and 4 250 (4 205-4 294)µg/L, which showed significant statistical differences (F = 233.68, P < 0.01). The blood Zn content of people in eastern China (3 938 µg/L) were significantly lower than it in middle (4 237 µg/L)and western China (4 105 µg/L) (F = 53.16, P < 0.01). In addition, the study also compared the relation between content of Cu and Zn and the frequency of eating seafood. The results found that the frequency of eating seafood could influence the content of Cu and Zn (Cu: F = 13.54, P < 0.01; Zn: F = 200.20, P < 0.01).

CONCLUSIONThe contents and distributions of Cu and Zn in blood differs among people from different groups in ages, genders and regions. The baseline data of this study provided reliable scientific evidence for further research.

Adolescent ; Adult ; Child ; China ; epidemiology ; Copper ; blood ; Cross-Sectional Studies ; Female ; Humans ; Male ; Middle Aged ; Young Adult ; Zinc ; blood

OBJECTIVETo assess the levels of polycyclic aromatic hydrocarbons monohydroxy metabolites in urine of general population in China among 8 provinces, provide the baseline of the metabolites in the general population.

METHODSFrom 2009 to 2010, 18 120 subjects of general population aged 6-60 years old were recruited from 24 areas among 8 provinces in east, west and central areas of China mainland by cluster random sampling. The information of the living environment and health condition were collected by questionnaire and spot urine samples were collected, 4 680 urine samples were analysed by high performance liquid chromatography with tandem mass spectrometry, and monohydroxy metabolites distribution in urine among groups of gender and ages were analysed.

RESULTSGeometric means (GM) of 2-naphthol, 1-naphthol, 3-phenanthrol and 1-hydroxypyrene concentration in urine (95%CI) were 1.85 (1.75-1.95), 1.55 (1.50-1.61), 0.57 (0.54-0.59) and 0.82 (0.78-0.85) µg/L, respectively;and median are 2.44, <0.50, 0.72 and 0.90 µg/L, respectively. The concentration between male and female were significantly different (P < 0.01), and the concentration among the groups of population were significantly different (P < 0.01), the GM of 2-naphthol among the groups of population aged 6-12, 13-16, 17-20, 21-30, 31-45 and 46-60 years old were 1.60, 1.56, 1.69, 2.23, 1.91 and 1.86 µg/L (χ(2) = 17.90, P < 0.01), the GM of 1-naphthol in the groups were 1.30, 1.16, 1.53, 1.68, 1.80 and 1.52 µg/L (χ(2) = 76.22, P < 0.01), the GM of 3-phenanthrol in the groups were 0.78, 0.76, 0.55, 0.42, 0.50 and 0.99 µg/L (χ(2) = 66.48, P < 0.01), the GM of 1-hydroxypyrene in the groups were 0.77,0.64, 1.00, 0.84, 0.84 and 0.57 µg/L (χ(2) = 51.48, P < 0.01), respectively.

CONCLUSIONThe distribution of monohydroxy metabolites levels in urine of general population were different, it provided a basic data for the further study of polycyclic aromatic hydrocarbons biomonitoring in the population.

Adolescent ; Adult ; Child ; China ; epidemiology ; Cross-Sectional Studies ; Environmental Exposure ; Female ; Humans ; Male ; Middle Aged ; Naphthols ; urine ; Polycyclic Aromatic Hydrocarbons ; urine ; Pyrenes ; urine ; Sentinel Surveillance ; Young Adult