The list of occupational diseases reflecting the latest advances in the identification and recognition of occupational diseases, and providing guidance on the protection of workers' health rights and interests and the prevention, recording, notification and compensation of related occupational diseases. Diagnostic criteria for occupational diseases are an important basis for making diagnoses attributable to occupational diseases, and provide a theoretical basis for health monitoring of occupational groups and occupational hygiene supervision. This thesis starts with the definition of the occupational disease elaborates in detail the development history of list of occupational diseases in International Labour Organization (ILO) , compares the list of occupational diseases in China (2013 version) with the list of occupational diseases in international (2010 version) , and then introduces in detail the latest diagnostic standards of the major occupational diseases. And finally, it puts forward relevant suggestions on the list and diagnostic level of China's occupational diseases, so as to provide certain insights for the further improvement of the list and diagnostic standards of occupational diseases.

The list of occupational diseases reflecting the latest advances in the identification and recognition of occupational diseases, and providing guidance on the protection of workers' health rights and interests and the prevention, recording, notification and compensation of related occupational diseases. Diagnostic criteria for occupational diseases are an important basis for making diagnoses attributable to occupational diseases, and provide a theoretical basis for health monitoring of occupational groups and occupational hygiene supervision. This thesis starts with the definition of the occupational disease elaborates in detail the development history of list of occupational diseases in International Labour Organization (ILO) , compares the list of occupational diseases in China (2013 version) with the list of occupational diseases in international (2010 version) , and then introduces in detail the latest diagnostic standards of the major occupational diseases. And finally, it puts forward relevant suggestions on the list and diagnostic level of China's occupational diseases, so as to provide certain insights for the further improvement of the list and diagnostic standards of occupational diseases.

Alfalfa(Medicago sativa L.)is the most important legume forage crop worldwide with high nutritional value and yield.For a long time,the breeding of alfalfa was hampered by lacking reliable information on the autotetraploid genome and molecular markers linked to important agro-nomic traits.We herein reported the de novo assembly of the allele-aware chromosome-level genome of Zhongmu-4,a cultivar widely cultivated in China,and a comprehensive database of genomic variations based on resequencing of 220 germplasms.Approximate 2.74 Gb contigs(N50 of 2.06 Mb),accounting for 88.39％of the estimated genome,were assembled,and 2.56 Gb contigs were anchored to 32 pseudo-chromosomes.A total of 34,922 allelic genes were identified from the allele-aware genome.We observed the expansion of gene families,especially those related to the nitrogen metabolism,and the increase of repetitive elements including transposable elements,which probably resulted in the increase of Zhongmu-4 genome compared with Medicago truncatula.Population structure analysis revealed that the accessions from Asia and South America had rela-tively lower genetic diversity than those from Europe,suggesting that geography may influence alfalfa genetic divergence during local adaption.Genome-wide association studies identified 101 sin-gle nucleotide polymorphisms(SNPs)associated with 27 agronomic traits.Two candidate genes were predicted to be correlated with fall dormancy and salt response.We believe that the allele-aware chromosome-level genome sequence of Zhongmu-4 combined with the resequencing data of the diverse alfalfa germplasms will facilitate genetic research and genomics-assisted breeding in variety improvement of alfalfa.

BACKGROUND: Microglia plays an indispensable role in the pathological process of sleep deprivation (SD). Here, the potential role of microglial CX3C-chemokine receptor 1 (CX3CR1) in modulating the cognition decline during SD was evaluated in terms of microglial neuroinflammation and synaptic pruning. In this study, we aimed to investigat whether the interference in the microglial function by the CX3CR1 knockout affects the CNS's response to SD. METHODS: Middle-aged wild-type (WT) C57BL/6 and CX3CR1-/- mice were either subjected to SD or allowed normal sleep (S) for 8 h to mimic the pathophysiological changes of middle-aged people after staying up all night. After which, behavioral and histological tests were used to explore their different changes. RESULTS: CX3CR1 deficiency prevented SD-induced cognitive impairments, unlike WT groups. Compared with the CX3CR1-/- S group, the CX3CR1-/- SD mice reported a markedly decreased microglia and cellular oncogene fos density in the dentate gyrus (DG), decreased expression of pro-inflammatory cytokines, and decreased microglial phagocytosis-related factors, whereas increased levels of anti-inflammatory cytokines in the hippocampus and a significant increase in the density of spines of the DG were also noted. CONCLUSIONS These findings suggest that CX3CR1 deficiency leads to different cerebral behaviors and responses to SD. The inflammation-attenuating activity and the related modification of synaptic pruning are possible mechanism candidates, which indicate CX3CR1 as a candidate therapeutic target for the prevention of the sleep loss-induced cognitive impairments.
Animals ; Cognitive Dysfunction ; Mice ; Mice, Inbred C57BL ; Microglia ; Neuroinflammatory Diseases ; Sleep Deprivation

Objective:To explore the risk factors of bladder recurrence in patients with upper urinary tract urothelial carcinoma (upper tract urothelial carcinoma, UTUC).Methods:We retrospectively analyzed the data of 815 patients underwent radical nephroureterectomy for upper tract urothelial carcinoma between June 2009 to June 2019.There were 519 males and 340 females, aged from 26-93 years old(average 66.5±9.6 years old). 396 patients were renal pelvic caicinoma.463 patients were ureteral caicinoma.675 patients were accompanied with hydronephrosis.664 patients were accompanied with preoperative gross hematuria. Preoperative diagnostic ureteroscopy was performed in 323 cases.283 patients had the history of smoking.48 patients were con-comitant with bladder carcinoma at the first diagnosis. Univariate analysis and logistic multivariate regression analysis were used to investigate the risk factors for bladder recurrence after UTUC radical surgery.Results:Among the 859 patients, 407 (47.4%) had low-stage tumor (T is/T a/T 1), 452 (52.6%) had high-stage tumor (T 2-T 4), 110 (12.8%) had low-stage tumor (G 1/G 2), and 749 (87.2%) had high-stage tumor (G 3). 126 (17.2%) of 859 patients had relapse during the follow-up period, the average follow-up time was 17 months, the median recurrence time was 12 months, 101(80.1%) of the relapse occurred within 2 years after operation. In univariate analysis, lower tumor stage ( P=0.047), higher tumor grade ( P=0.043), preoperative hematuria symptom ( P=0.023) and preoperative diagnostic ureteroscopy ( P=0.002) were closely related to bladder recurrence. Taking the above factors into the logistic multivariate regression analysis showed that tumor staging T is/T s/T 1 ( B=0.476, P=0.019), tumor grade G 3( B=0.848, P=0.024), preoperative hematuria symptom ( B=0.521, P=0.048), preoperative diagnostic ureteroscopy( B=0.521, P=0.002) were independent risk factors of postoperative recurrence of bladder. Conclusion:lower tumor stage, higher tumor grade, preoperative hematuria symptom and preoperative diagnostic ureteroscopy are the independent risk factors of postoperative bladder recurrence in patients with UTUC. Routine intravesical chemotherapy should be performed in patients with UTUC with the above risk factors, and routine diagnostic ureteroscopy is not recommended.

Objective: To analyze Internet behaviors of children and adolescents and their influencing factors, and to provide scientific basis for health education guidance and prevention measures. Methods: A stratified cluster sampling method was used. From January to June 2019, 30 955 primary school students in 16 provinces (municipalities), from eastern, central, and western economic zones of China were selected to conduct a questionnaire survey, regarding general demographics, diet and exercise, tobacco, alcohol and sleep, Internet and electronics usage, etc. Results: Among them, 43.1% of students had never been online with girls (44.7%) higher than boys (41.8%)(χ2=21.04, P<0.01); 1.3% of students reported online time for more than 4 hours a day, boys were significantly higher than girls(χ2=15.87, P<0.01); Internet addiction was detected in 2.4% of elementary school students, with boys (3.0%) higher than girls(1.7%)(χ2=331.77, P<0.01), and the trend increases with grade. With sixth grade (3.3%) were significantly higher than children from the first grade (0.8%) and other grades(χ2=163.96, P<0.01). Children’s tendency to Internet addiction was 11.9%, of which boys were 13.0% and girls were 10.6%, boys were significantly higher than girls(χ2=117.66, P<0.01). Pearson correlation analysis revealed that, after controlling gender age, boarding school, family relationship, single parents and regrouped families, smoking, drinking sugary drinks, eating fried foods, and left-behind were positively related to Intenet addiction(r=0.06, 0.07, 0.27, 0.44, 0.07, 0.11, 0.09, P<0.01), while medium and high intensity sports, effective physical education, health education in school, AIDS education and parental restrictions on TV and computer games, were negatively associated with internet addiction(r=-0.74, -0.65, -0.04, -0.05, -0.63, P<0.01). Conclusion The internet addiction of Chinese primary school students is common and increases by year. High-intensity, high-density sports, effective physical education, and health education could help prevent Internet addiction among children.

OBJECTIVE：To study the effects of stilbene glucoside （TSG）on the proliferation and estrogen receptor （ER）of human breast cancer T- 47D cells ，and to explore its estrogen-like effect and potential mechanism. METHODS ：Taking ER positive human breast cancer T- 47D cells as subjects ，using β-estradiol（β-E2，1×10－8 mol/L）as positive control ，CCK-8 assay was used to detect the cell proliferation after treated with different concentrations of TSG （1×10－8，1×10－7，1×10－6，1×10－5，1×10－4 mol/L）for 24，48，72 h；the cell proliferation rate was calculated. Western blotting assay and RT-PCR methods were adopted to detect the protein and mRNA expression of ER-α and ER-β in cells after treated with low，medium and high concentrations of TSG （1×10－8， 1×10－6，1×10－4 mol/L）for 48 h. RESULTS ：After treated with different concentrations of TSG for 24，48，72 h，the cell proliferation rate of each administration group at each time point （except for β-E2 group at 48 h）increased significantly ，compared with blank group ；those of TSG groups （1×10－5，1×10－6，1×10－7 mol/L）were significantly higher than β-E2 group（P＜0.05 or P＜0.01）. After treated with low ，medium and high concentrations of TSG for 48 h，protein and mRNA expression of ER-α and ER-β in cells were increased significantly，compared with blank group （P＜0.05 or P＜0.01）；protein expression of ER-β in TSG low concentration group ，mRNA expression of ER-α in TSG groups as well as mRNA expression of ER-β in TSG low and high concentration groups were significantly higher than β-E2 group（P＜0.05 or P＜0.01）. CONCLUSIONS ：TSG can induce the in vitro proliferation of T- 47D cells and exert estrogen-like effects by promoting protein and mRNA expression of ER-α and ER-β， which is stronger than that of β-E2 at a certain concentration.

OBJECTIVE: To analyze the hotspots and related situations of pneumoconiosis research in China from 2001 to2017. METHODS: China National Knowledge Infrastructure and Wanfang Data were used to retrieve relevant literature on China's pneumoconiosis research from 2001 to 2017. Bibliometrics was used to analyze the distribution of publication time,regions,hotspots,authors and their institutions,carrier journals,keywords,etc. RESULTS: A total of 10 208 literature articles on pneumoconiosis research were screened. The number of published literature in 2001-2017 showed an upward trend year by year( P < 0. 01). Provinces in the Eastern area have the largest number of publications. The areas that have the largest number of publications were in Shandong Province,Beijing City and Hebei Province,followed by Anhui Province,Guangdong Province,Jiangsu Province,Liaoning Province,Shanxi Province and Henan Province. Beijing City,Hebei Province,Tianjin City,Liaoning Province,Anhui Province,Jiangsu Province,Hubei Province and Shanghai City are the hotspots for research on pneumoconiosis. The publications were seen in 1 173 journals. Five occupational medical professional periodicals such as Occupation and Health,Chinese Journal of Industrial Hygiene and Occupational Diseases,China Occupational Medicine,Chinese Journal of Industrial Medicine and Industrial Health and Occupational Diseases publish' the most literature on pneumoconiosis research,accounting for 26. 99% of the effective literature.Occupational disease prevention institutions and hospitals are the main organizations for publishing literatures. The focuses of pneumoconiosis research are silicosis and coal worker's pneumoconiosis,etc. CONCLUSION: Generally,the literature on the research of pneumoconiosis in China from 2001 to 2017 is increasing and is focus on some specific hotspots.Pneumoconiosis research has been specialized. An important carrier for publishing research results has been formed.

OBJECTIVE： To investigate estrogen-like effect of tetrahydroxy stilbene glucoside （TSG） and its effects on the expression of estrogen receptor （ER） in uterus of sexually immature mice. METHODS： Totally 60 sexually immature Kunming mice were randomly divided into normal group， positive control group （estradiol valerate， 0.18 mg/kg）， TSG low-dose and high-dose groups （50， 150 mg/kg）， TSG low-dose and high-dose groups+estradiol valerate groups （same dose as medication alone group）. Normal group was given constant volume of water intragastrically， and administration groups were given relevant medicine 0.2    mL/10 g， once morning and night， for consecutive 5 d. The uterus index and body weight increase of mice in each group were determined and calculated the next day after the last administration. The contents of serum estrogen （E2， LH， FSH） were determined by ELISA. HE staining was used to observe the morphology characteristics of uterus， and uterine tube diameter and endometrial thickness were detected. The expression of ER（ER-α and ER-β） in uterus was detected by immunohistochemical staining. RESULTS： The myometrium of the mice in normal group was parallel and compact， the epithelium of the uterus was columnar， and the expression of ER-α and ER-β was low. The uterine tube diameter， endometrium and epithelium of mice in each administration group increased， thickened or proliferated in varying degrees， and the expression of ER-α and ER-β changed. Compared with normal group， uterus indexes （positive control group， TSG high-dose group， TSG+estradiol valerate groups）， the increase of body weight （positive control group， TSG high-dose groups， TSG low-dose+estradiol valerate group）， uterine tube diameter and endometrial thickness （positive control group， TSG low-dose group， TSG+estradiol valerate groups）， the expression of ER-α （positive control group， TSG+estradiol valerate groups） and the expression of ER-β （postive control group， TSG high-dose+estradiol valerate group）were increased significantly， while serum contents of LH （positive control group， TSG high-dose group） and FSH （TSG low-dose+estradiol valerate group） were decreased significantly （P＜0.05 or P＜0.01）. The uterus index， uterine tube diameter， endometrial thickness and the expression in ER-α and ER-β of TSG+estradiol valerate groups， the increase of body weight and serum content of E2 in TSG low-dose+estradiol valerate group were significantly higher than same TSG dose alone groups （P＜0.05 or P＜0.01）. The uterus index， uterine tube diameter， endometrial thickness and the expression of ER-α and ER-β in TSG groups， uterine tube diameter and the expression of ER-β in TSG+estradiol valerate groups， body weight increase of mice in TSG low-dose group were significantly lower than positive control group， while serum content of LH in TSG+estradiol valerate groups were significantly higher than positive control group （P＜0.05 or P＜0.01）. CONCLUSIONS： TSG can increase uterus indexes and body weight of sexually immature mice to certain extent， regulate estrogen level， increase the diameter of uterine tube and endometrial thickness and up-regulate the expression of ER in the uterus， showing certain estrogen-like effect， which is weaker than that of estradiol valerate. Combined use of them may antagonize the effect of estradiol valerate.

OBJECTIVE： To study the effects of processed Polygonum multiflorum containing serum on the proliferation and the expression of estrogen receptor （ER） of human breast cancer T-47D cells， and to investigate its phytoestrogen （PE）-like effect. METHODS： Sexually immature SD rats were randomly divided into estradiol valerate （Ev） group （positive control， 0.12 mg/kg）， processed P. multiflorum low-dose and high-dose groups （0.75， 3 g/kg， by crude drug）， low-dose and high-dose processed P. multiflorum+Ev groups （same dose as single drug group）， with 10 rats in each group. Blank group was given constant volume of water intragastrically， and administration groups were given relevant medicine intragastrically； once day and night， for consecutive 4 days. Two hours after last administration， blank serum and containing serum were prepared. T-47D cells were also randomly divided into blank group， Ev group， low-dose and high-dose processed P. multiflorum groups， low-dose and high-dose processed P. multiflorum+Ev groups， and then were cultured in medium which contained 20％ blank serum or drug containing serum. CCK-8 assay was used to detect proliferation rate （PR）. Western blotting assay and RT-PCR were used to detect the protein and mRNA expression of ER-α and ER-β. RESULTS： Compared with blank group， PR of administration groups [each administration group （24 h）， other administration groups （48， 72 h） except for high-dose processed P. multiflorum+Ev group] were increased significantly； high-dose processed P. multiflorum group （72 h） was significantly higher than Ev group， and low-dose processed P. multiflorum+Ev group （72 h） was significantly higher than the same-dose processed P. multiflorum group； high-dose processed P. multiflorum+Ev group （72 h） was significantly lower than the same-dose processed P. multiflorum group （P＜0.05 or P＜0.01）. Relative protein expression of ER-α in Ev group， high-dose processed P. multiflorum group and low-dose processed P. multiflorum+Ev group， relative mRNA expression of ER-α and protein expression of ER-β in administration groups， relative mRNA expression of ER-β in Ev group， low-dose processed P. multiflorum group and processed P. multiflorum+Ev groups were all increased significantly. Relative protein and mRNA expression of ER-α in Ev group were significantly higher than processed P. multiflorum groups and combination groups. Relative protein and mRNA expression of ER-β in Ev group were significantly lower than low-dose processed P. multiflorum+Ev group， but relative mRNA expression of ER-β was significantly higher than processed P. multiflorum groups and high-dose processed P. multiflorum+Ev group. Relative protein and mRNA expression of ER-α and ER-β in low-dose processed P. multiflorum+Ev group as well as relative mRNA expression of ER-β in high-dose processed P. multiflorum+Ev group were significantly higher than the same-dose processed P. multiflorum group. Relative protein and mRNA expression of ER-α in high-dose processed P. multiflorum+Ev group were significantly lower than the same-dose processed P. multiflorum group （P＜0.05 or P＜0.01）. CONCLUSIONS： The processed P. multiflorum containing serum can promote the proliferation of human breast cancer T-47D cells， and play the PE-like role through promoting protein and mRNA expression of ER-α and ER-β. However， the above effects are weaker than estrogen， and the combination of the two may antagonize the effect of estrogen.