[Abstract] Objective: To explore the expression patterns of melanoma lineage antigens and nuclear antigen Ki-67 and their correlations with survival in melanoma patients. Methods: A retrospective analysis was conducted to analyze the pathological data of melanoma patients treated at the Department of Melanoma, Peking University Cancer Hospital from February 2008 to August 2020, mainly including the expression patterns of melanoma lineage antigens (S-100, HMB-45, Melan-A) and Ki-67, demographics, clinical features and survival. The correlation between expression patterns of melanoma lineage antigens, Ki-67 and melanoma-specific survival (MSS) was analyzed. Results: In total, 603 patients were included in this study. The median follow-up time was 47.4 months. The positive rates of S-100, HMB, and Melan-A were 92.8%, 92.1% and 90.0%, respectively. The percentages of patients with melanoma lineage antigen scores (S-100, HMB-45 and Melan-A was scored each, as 1 when positive and 0 when negative) of 0, 1, 2, and 3 were 0.5%, 5.0%, 15.6%, and 78.8%, respectively. The percentages of patients with Ki-67 scores of 0, 1, 2, and 3 were 43.0%, 36.3%, 16.3%, and 4.5%, respectively. Ki-67 was highly expressed in mucosal and progressive melanomas. In a multivariate analysis, Ki-67 expression was an independent prognostic factor for poorer MSS (HR=1.506, 95%CI: 1.248-1.818, P<0.001) as the incidence of MSS event increased by 50% per 25% increase in Ki-67 expression, whereas there was no statistical correlation between melanoma lineage antigen expression and MSS (HR=0.991, 95%CI: 0.759-1.293, P=0.94). Conclusion: High expressions melanoma lineage antigens are ubiquitous in melanoma tissues, and Ki-67 is an independent prognostic factor for MSS.

Objective:To explore the prognostic value of PD-L1 expression level in patients with metastatic renal cell carcinoma (mRCC).Methods:The clinicopathological and survival data of patients with mRCC in our hospital from Jan 2014 to Apr 2016 were retrospectively analyzed including 46 males and 15 females. The median age of these patients was 56 years(range: 29-75 years), with 41 patients ≤60 years and 20 patients >60 years. The baseline data before the systemic therapy showed 36 patients(59.0%)had 1 metastatic organ and 25 patients (41.0%) had equal or more than 2 organs to be metastasized. Among them, 17 patients(27.9%)had lung metastasis and 54 patients(88.5%)had liver metastasis. Abnormal baseline LDH occurred in 4 patients and 52 patients had normal LDH. Favorite and intermediate risk patients categorized by MSKCC risk stratification accounted for 59.6%(34 patients)and 40.4%(23 patients), respectively. Six patients(9.8%)experienced distant metastasis at initial diagnosis, with 4 of them undergoing primary site resection, and the other 55 patients undergoing radical nephrectomy. PD-L1 expression was detected by the immunohistochemical staining method. PD-L1 staining rate ≥1% detected on the tumor cell membrane was defined as positive expression. The correlation between PD-L1 expression and clinicopathological characteristics were compared. Kaplan-Meier method and log-rank test were used to compare the differences about DFS and OS under different factors. Cox proportional hazards regression model is used for multivariable analysis of survival data.Results:The detailed pathological types of the 61 patients with renal cell carcinoma were classified as 53 clear cell carcinomas, 3 papillary carcinomas, 1 collecting duct carcinoma, 2 translocation renal cell carcinomas and 2 being unclassified. There were 4, 20, 19 and 9 patients categorized as WHO/ISUP nuclear grade 1, 2, 3 and 4, and 26, 12, 20 and 2 patients were categorized as T 1, T 2, T 3 and T 4 stage, respectively. Five patients had regional lymph node metastasis(N+), and the other 56 patients had no regional lymph node metastasis(N-). The numbers of patients categorized as stage Ⅰ, Ⅱ, Ⅲ and Ⅳ diseases according to TNM staging system were 20, 11, 21 and 8, respectively. The total PD-L1 positive rate was 24.6%(15/61). The corresponding PD-L1 expression rate of patients with WHO/ISUP nuclear grade 1-4 were 0(0 patient), 5.0%(1 patient), 31.6%(6 patients)and 44.4%(4 patients), respectively; With the increasing WHO/ISUP nuclear grade, the positive rate of PD-L1 gradually escalated with a linear correlation ( P=0.006). The PD-L1 expression of the normal and abnormal LDH group were 19.2%(10 patients)and 75.0%(3 patients), respectively, with significant difference( P=0.035). Univariate analysis of disease-free survival time(DFS)showed that the prognostic factors include PD-L1( P=0.045), age group( P=0.014), WHO/ISUP nuclear grade( P<0.001), T stage( P=0.015), N stage( P=0.026)and TNM stage( P=0.005). However multivariate analysis only suggested WHO/ISUP nuclear grade as the independent prognostic factors for DFS( HR=1.8, 95% CI 1.1-2.9, P=0.018). Either in univariate or multivariate analysis, PD-L1 was not a prognostic factor for overall survival (OS)of mRCC patients(univariate analysis: P=0.154; multivariate analysis: P=0.902). The independent prognostic factors of OS include WHO/ISUP nuclear grade( HR=3.0, 95% CI 1.1-8.0, P=0.033)and MSKCC risk stratification( HR=5.9, 95% CI 1.2-29.7, P=0.03). Conclusions:This study showed that the higher the WHO/ISUP nuclear grade of patients with mRCC, the higher the positive rate of PD-L1. PD-L1 expression was not the independent prognostic factor for DFS or OS of mRCC.

Objective To investigate the influence of different water-improving defluoridation projects and different water-improving years on children's dental fluorosis,and to provide a scientific basis for further defluoridation of drinking water.Methods Totally 1/4 endemic fluorosis villages in all agricultural-related areas of Tianjin were selected by random sampling method from 2016 to 2017.The situation of water-improving defluoridation project was investigated in these villages.The ways of water improvement included municipal water supply,double pipe network,barreled water,low fluorine well and centralized water supply.The years of water improvement were ＞ 15,＞ 10-15,5-10,and ＜ 5 years,respectively.Totally 821 water samples (surface water,barreled water and groundwater) were collected.Fluoride ion selective electrode method was used for determination of water fluorine content.According to the "Diagnosis of Dental Fluorosis" (WS/T 208-2011),the prevalence of dental fluorosis in children aged 8 to 12 was examined.Results A total of 524 villages with drinking water endemic fluorosis and 35 870 children aged 8 to 12 were investigated in Tianjin.The water improvement rate was 73.28％ (384/524).Water fluoride qualified village accounted for 53.24％ (279/524).The detection rate of dental fluorosis was 47.98％ (17 209/35 870),the detection rate of dental fluorosis was different with different water improvement methods (x2 =1 955.742,P ＜ 0.05).Children's dental fluorosis detection rate in the area of municipal water supply was lower (33.19％,4 121/12 416),while that in double pipe network reconstruction area was 43.37％ (995/2 294).Children's dental fluorosis detection rates in the areas of barreled water supply,low fluoride well and centralized water supply were higher (58.47％,6 268/10 720;66.84％,1 719/2 572;53.75％,623/1 159).The median of water fluoride in the renovated area of municipal water supply was 0.24 mg/L,and the proportion of villages with water fluoride ≤ 1.2 mg/L was 100.00％ (133/133).With the increase in water-improving years (more than 10 years),children's dental fluorosis prevalence [＞ 15,＞ 10 ～ 15 years were 17.41％ (428/2 459),14.19％ (266/1 875)] in the areas of municipal water supply reached the control standards (≤30％).Conclusions The improvement of the municipal water supply network is thorough,which can meet the requirement of continuously ensuring the safety of drinking water for residents,especially those over 10 years.Other forms of water-improving need to be further optimized.

Objective To explore the thyroid volume of children aged 8-10 years in non-iodine high area and iodine high area of Tianjin and to analyze the relationship between thyroid volume and urinary iodine level.Methods In 2016-2017,a cross-sectional study was conducted in non-iodine high area and iodine high area in Tianjin.Totally 356 and 199 children aged 8-10 years were selected,respectively.The urine samples of children were collected and the iodine concentration in urine was measured by "As3+-Ce4+ catalytic spectrophotometry".The thyroid volume was monitored by B ultrasonic method.Results The medians of urinary iodine in the 8,9 and 10 years old age groups in iodine high area (500.00,443.00,407.00 μg/L) were higher than those of non-iodine high area (189.39,168.35,189.90 μg/L,Z =7.162,7.536,6.126,P ＜ 0.05).The thyroid volume of children aged 8 and 9 years in iodine high area (2.81,2.91 ml) was higher than that in non-iodine high area (2.31,2.44 ml,Z =3.474,3.264,P ＜ 0.05).There was a weak correlation between urinary iodine and thyroid volume (r =0.109,P ＜ 0.05).Conclusion The urinary iodine level and thyroid volume of children aged 8 and 9 in iodine high areas are higher than those in non-iodine high areas.

Objective: To investigate the effects of fluoride exposure on the thyroid hormone level and intelligence in rats and to investigate the biomarkers of intellectual impairment induced by high fluoride exposure. Methods: A total of 24 clean healthy Sprague-Dawley rats were randomly divided into control group (tap water containing 0.344 mg/L fluoride) and low-, medium-, and high-fluoride exposure groups (tap waters containing 10, 50, and 100 mg/L sodium fluoride, respectively). One male rat was cohabited with two female rats in the same group. After the offspring rats were weaned, 12 offspring rats (male/female ratio=1∶1) with a similar body weight in each group were subjected to the same treatment for the parental offspring. The offspring rats were sacrificed on the 60th day after birth. The weight of offspring rats was measured. Serum thyrotropin (TSH) , free triiodothyronine (FT₃) , and free thyroxine (FT₄) levels were measured by enzyme-linked immunosorbent assay. The learning and memory abilities of the rats were evaluated by Morris water maze test. The expression of mitochondrial fission 1 (Fis1) and mitofusin 1 (Mfn1) in blood was measured by Western blot. Results: The offspring rats in the medium-and high-fluoride exposure groups had significantly lower serum TSH and FT₄ levels than those in the control group (P<0.05). The place navigation test showed that the offspring rats in the medium-and high-fluoride exposure groups had significantly longer escape latency than those in the control group (P<0.05) , and the high-fluoride exposure group had a significantly longer escape distance than those in the control group (P<0.05). The spatial probe test showed that the offspring rats in the low-, medium-, and high-fluoride exposure groups had significantly shorter swimming time and distance in the target quadrant and total swimming time and distance than those in the control group (P<0.05). Compared with the offspring rats in the control group, those in the low-, medium-, and high-fluoride exposure groups had significantly higher expression of Fis1 (P<0.05) , and those in the low- and medium-fluoride exposure groups had significantly higher expression of Mfn1 (P<0.05) . Conclusion High fluoride exposure can reduce the secretion of thyroid hormone and the abnormality of mitochondrial dynamics in peripheral lymphocytes may provide a clue to identifying the biomarkers of intellectual impairment induced by fluoride exposure.

OBJECTIVETo evaluate the association of colorectal adenoma with metabolic syndrome (MS) and relevant parameters.

METHODSClinical data of 289 subjects who underwent screening colonoscopy in the University of Hong Kong-Shenzhen Hospital from January 2014 to June 2015 were retrospectively analyzed, including 130 normal subjects (normal group) and 159 cases with colorectal adenoma confirmed by pathology(adenoma group). Levels of MS-associated parameters were compared between the two groups, and the association of metabolic diseases with colorectal adenoma was examined.

RESULTSThe gender, smoking and drinking habit, regular physical activity, family history of colorectal cancer, and consumption history of long-term non-steroidal anti-inflammatory drugs were not significantly different between two groups (all P>0.05). As compared to normal group, adenoma group had higher body mass index (BMI) [(23.5±3.2) kg/m(2) vs. (22.7±2.8) kg/m(2), t=1.97, P=0.050], larger abdominal circumference [(83.4±10.3) cm vs. (79.6±13.8) cm, t=2.46, P=0.015], higher serum high-density lipoprotein level [(1.3±0.3) mmol/L vs. (1.2±0.3) mmol/L, t=2.03, P=0.044], and higher serum cholesterol [(5.4±1.0) mmol/L vs. (5.0±1.1) mmol/L, t=2.39, P=0.018]. No significant difference was demonstrated in comparing hip circumference and waist-hip ratio, as well as serum fasting glucose and triglyceride(all P>0.05). Higher incidence of colorectal adenoma was found in subjects with MS [69.8%(37/53) vs. 1.7%(122/236), P=0.017], overweight or obesity [65.1% (56/86) vs. 50.7%(103/203), P=0.025], hypertension [67.3%(37/55) vs. 52.1%(122/234), P=0.046] and hypercholesterolemia [66.7%(64/96) vs. 49.2%(95/193), P=0.005].

CONCLUSIONSMetabolic syndrome increased the risk of developing colorectal adenoma. The mechanism may be related to higher serum cholesterol and high density lipoprotein, which may lead to the elevated catabolism of serum cholesterol. Screening colonoscopy should be performed for patients diagnosed as metabolic syndrome, especially for those with central obesity and hypercholesterolemia, thus early diagnosis and treatment of colorectal adenoma may be available.

Adenoma ; epidemiology ; Blood Glucose ; chemistry ; Body Mass Index ; Case-Control Studies ; Colonoscopy ; Colorectal Neoplasms ; epidemiology ; Humans ; Hypercholesterolemia ; epidemiology ; Hypertension ; epidemiology ; Mass Screening ; Metabolic Syndrome ; epidemiology ; Obesity ; epidemiology ; Overweight ; epidemiology ; Retrospective Studies ; Triglycerides ; blood

Objective To study the intake of iodine and iodine nutritional status of adults and provide a scientific basis for choosing appropriate salt iodine content in the region.Methods By using multi stage random sampling method,according to the four corners of 4 directions,4 non water iodine counties or districts were selected from Nankai District,Jixian County,Dagang District and Hangu District.Totally 1 to 4 administrative villages were selected (neighborhood committees) from each district or county as the survey points.Ten to 15 households were selected from each survey points.All the members more than 18 years old of each household were investigated (excluding pregnant and lactating women).Of the 225 households,404 people,salt iodine of the family,urinary iodine and water iodine were detected.The questionnaire survey was used to investigate the daily salt intake of residents per capita.The daily intake of iodine was calculated by the method of dietary frequency.Salt iodine content was detected by direct titration method;iodine in water was detected by cerium sulfate catalytic spectrophotometry;urinary iodine was detected by arsenic cerium catalytic spectrophotometry.Results A total of 24 drinking water samples were tested,the median water iodine was 8.0 μg/L.A total of 225 salt samples and 404urine samples were tested,the medians of family salt and urinary iodine were 23.30 mg/kg and 149.0 μg/L,respectively.Investigation was done on salt intake and dietary intake of 393 people,the per capita consumption of salt intake was (11.45 ± 5.70) g/d.Salt supplied 148.75 μg/d iodine and food supplied 82.47 μg/d iodine.The total contribution rate of iodized salt to the total iodine intake was 68.99％ (193.18/280.00) in the population of iodized salt consumer.The value of urinary iodine and iodine intake were correlated (r =0.170,P ＜ 0.05).Conclusions The adult iodine nutrition in Tianjin city is in the appropriate level.Iodized salt is the main source of iodine intake for adults,so salt iodine is a indispensable iodine nutrition source for adults.

Objective:To study the role of activin A in regulation of neutrophil function by detecting activin receptor expression and cellular activities.Methods:Peritoneal neutrophils were isolated in mouse.After the neutrophils were stimulated with activin A,the expression of ActRⅡA on neutrophils was examined by immunofluorescence and flow cytometry.Expression of Smad3 in neutrophils was analyzed by Western blot.Assays of neutrophils function were performed by detecting respiratory burst, production of NO and phagocytosis.Results:The isolated cells were composed of more than 90% peritoneal neutrophils.ActRⅡA was expressed on mouse neutrophils and Gr-1/ActRⅡA double-positive cells were 41.1%.Activin A promoted Smad3 phosphorylation in neutrophils,increased the production of ROS and O2-(P<0.05),enhanced secretion of NO and phagocytosis of mouse neutrophils(P<0.01),and promoted fluorescent microsphere phagocytosis of neutrophils by flow cytometry ( P<0.01 ) .Conclusion: Activin receptor and activin signaling protein were expressed on mouse neutrophils,activin A might play an important regulatory role in activation and function of neutrophils.

objective To understand the baseline data of mortality from malignant tumor from 2006 to 2009 around Hongyanhe Nuclear Power Plant in Wafangdian City,Liaoning Province,so as to provide scientific basis for evaluating the impact of normal operation of nuclear power plant on the health of the residents nearby.Methods Thirty small towns near Hongyanhe Nuclear Power Plant were divided into 5 investigated areas according to the distances away therefrom(0.,10.,20-,30-,and 40-km).The data about from malignant tumor were obtained from the Center for Disease Control and Prevention of Wafangdian.The mortality distribution of difierent malignant tumors was analyzed,including the radiosensitive malignant tumors,especially leukemia,breast cancer,and thyroid gland cancer in different area,gender,and age groups.Results The mortality from malignant tumor was 151.97/105,and the standardized mortality rate(SMR)was 97.76/105.The mortality from malignant tumor among the males was 188.28/105(with the SMR of 116.76/105),and that among the females was 113.47/105(with the SMR of 75.89/105).with a sex ratio of 1.71.The first five cancers in the rank of death causes were lung,liver,stomach,colorectal,and esophageal cancers with mortality of 46.19/105,23.51/105,20.30/105,8.06/105 and 5.45/105,respectively.The mortality from mal.ignant tumor in the areas around the nuclear power plant from the near to the distant were 99.85/105, 137.40/105,138.73/105,156.30/105,and 154.16/105,respectively.The mortality from radiosensitive malignant tumors,leukemia,breast cancer,and thyroid gland cancer were 4.57/105,4.06/105,and 0.26/105,respectively.Conclusions Lung cancer and digestive tract malignant tumors are the main causes of death from malignant tumors in Wafangdian area before the nuclear power plant began to operate.There are no significant differences in the mortality distribution of malignant tumors among different areas,genders,and age groups.There are not significant differences in the mortality distribution of leukemia and breast cancer among different areas and age groups.

Objective To prepare anti-activin receptor-interacting protein 1 (ARIP1) polyclonal antibody.Methods The GST-ARIP1 fusion protein was expressed in E.coli BL21.A polyclonal antibody against ARIP1 was obtained by immunizing a rabbit with the purified GST-ARIP1 and the localization of mature ARIP1 protein in mouse brain tissues was detected by immunohistochemistry using the prepared anti-ARIP1 antibody.Results Anti-ARIP1 polyclonal antibody could bind specifically with recombinant ARIP1,but not recombinant ARIP2.Immunohistochemical staining showed that ARIP1 mainly expressed in hypothalamus and hippocampus using the prepared anti-ARIP1 antibody.Conclusion The polyclonal antibody against ARIP1 has been successfully prepared and can be used to do immunohistochemical analysis for ARIP1 protein expression.