Study on the biological exposure limit of whole blood chromium in occupational hexavalent chromium compounds exposed population / 中国职业医学

ObjectiveTo analyze the exposure-response relationship of peripheral whole blood chromium level and lung function as well as genetic toxicity indicators in workers exposed to hexavalent chromium [Cr(Ⅵ)] compounds, and to propose a biological exposure limit of whole blood chromium for soluble Cr(Ⅵ) compounds-exposed workers. Methods A total of 515 workers from a dynamic occupational Cr(Ⅵ) compounds-exposed cohort in an enterprise from 2010 to 2017 were selected as the research subjects using a retrospective cohort study. A total of 918 followed-up results of research subjects and baseline data of a cohort were analyzed based on bibliometric analysis. The results include lung function tests, whole blood chromium level detected by inductively coupled plasma-mass spectrometry, urinary 8-hydroxy-2′-deoxyguanosine (8-OHdG) detected by high performance liquid chromatography-tandem mass spectrometry, peripheral micronuclei frequency (MNF) detected by cytokinesis-block micronucleus assay, and mitochondrial DNA copy number (mtCN) detected by real-time fluorescence quantitative polymerase chain reaction. Results The results of bibliometric analysis showed that domestic and foreign studies on biological monitoring of Cr(Ⅵ) compounds increased year by year in the past 30 years, and whole blood chromium levels had a good correlation with the occupational Cr(Ⅵ) compounds exposure. The geometric mean of whole blood chromium levels in males and females among the occupational Cr(Ⅵ) compounds exposure cohort was 2.77 and 1.79 μg/L, respectively. A turning point appeared in 6.00 μg/L chromium in whole blood of the exposure-response curve of whole blood chromium levels with lung function indicators and genetic toxicity indicators. For each unit increase in the natural logarithm-transformed whole blood chromium level, the forced expiratory volume in one second (FEV1) decreased by 0.05 L, the FEV1/forced-vital-capacity decreased by 0.67%, the peak expiratory flow decreased by 0.15 L/s, the maximal mid-expiratory flow decreased by 0.09 L/s, the MNF increased by 0.149‰, the urinary 8-OHdG increased by 0.090 μg/g, and the mtCN increased by 0.013. When the whole blood chromium level was >6.00 μg/L, there was a significant increase in urinary 8-OHdG, MNF, and mtCN (all P<0.01). Conclusion The level of whole blood chromium can be used as a biomarker for occupational exposure to soluble Cr(Ⅵ) compounds. The preliminary biological exposure limit is set at 6.00 μg/L for whole blood chromium in workers exposed to soluble Cr(Ⅵ) compounds.

Effects of titanium dioxide nanoparticles on circRNA expression profiles in human hepatocellular carcinoma cells HepG2 / 北京大学学报(医学版)

OBJECTIVE@#To investigate the effect of titanium dioxide nanoparticles (TiO2 NPs) on the expression profile of circular ribonucleic acid (circRNA) in human hepatocytes through in vitro cell experiments, and to attempt to understand the potential mechanism of hepatotoxicity through bioinformatics analysis.@*METHODS@#TiO2 NPs were characterized from the aspects of particle size, shape and agglomeration state. The cell counting kit-8 (CCK8) was used to detect the cytotoxicity of TiO2 NPs against human hepatocellular carcinoma cells (HepG2) after exposure to 0, 1.56, 3.13, 6.25, 12.5, 25, 50, 100, and 200 mg/L TiO2 NPs for 24 h or 48 h. The cells were treated at doses of 0 mg/L TiO2 NPs (control group) and 100 mg/L TiO2 NPs (treatment group), and collected after exposure for 48 h, and then RNA from the extracted cell samples was collected and sequenced. The differential circRNAs between the control and the TiO2 NPs treatment groups were screened, and then the enrichment pathway of the differential circRNA target gene was analyzed by multivariate statistics. According to the sequencing results, significantly altered genes and important genes in the significant enrichment pathways were screened, and real-time reverse transcription-polymerase chain reaction (real-time RT-PCR) was performed to verify the results.@*RESULTS@#TiO2 NPs were spherical anatase with a hydrated particle size of (323.50±85.44) nm and a Zeta potential of (-21.00±0.72) mV in a serum-free medium. The results of the CCK8 cytotoxicity assay showed that with the increase of TiO2 NPs concentration, cell viability gradually decreased. A total of 11 478 circRNAs were found by RNA sequencing. Compared with the control groups, TiO2 NPs treatment groups (100 mg/L) had a total of 89 differential circRNAs, of which 59 were up-regulated and 30 were down-regulated. Analysis of the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway showed that the targeted genes of differential circRNAs were mainly enriched in fatty acid degradation, Fanconi anemia pathway, and fatty acid metabolism. The expression levels of circRNA.6730, circRNA.3650 and circRNA.4321 were significantly different between the TiO2 NPs treatment group and the control group, which were consistent with the sequencing results.@*CONCLUSION@#TiO2 NPs can induce changes in circRNA expression profile, and epigenetics may play an important role in the mechanism of hepatotoxicity.

Robot-assisted Posterior Laparoscopic Modified "Single-position" Treatment for Upper Tract Urothelial Carcinoma:Report of 7 Cases / 中国微创外科杂志

Objective To evaluate the feasibitity of robot-assisted posterior laparoscopic modified"single-position"radical nephroureterectomy.Methods A retrospective analysis was made on 7 patients receiving robot-assisted posterior laparoscopic single-position radical nephroureterectomy between April 2022 and April 2023.The patients were in a fully healthy lateral position,and an artificial pneumoperitoneum was established.Trocars were placed at the right costal margin of the posterior axillary line,3-4 cm above the iliac crest of the midaxillary line,6-8 cm below the anterior axillary line,and 3-4 cm above the iliac crest of the midaxillary line near the outer edge of the musculus rectus abdominis,respectively.After the kidney was removed,the ureter was freed down to the iliac vessels,and then the main joint of the robot was reversed 180° for redocking.The ureter was continuously freed downwards to the bladder wall and the catheter was clamped.The bladder was opened after filling with indocyanine green and distilled water mixture.Then the fluid in the bladder was washed,the contralateral ureteral orifice was observed,the affected side of the ureter was resected,and the bladder incision was sutured by two layers with V-LOCK 2-0 sutures.The incision was extended under the right costal margin of the posterior axillary line and 3-4 cm above the iliac crest of the midaxillary line to remove the specimen.Results The operation was successfully completed in all the 7 cases.The surgical operation time was 155-263 min(mean,247.0 min)and the blood loss was 20-100 ml(mean,42.9 ml).The postoperative anal exhaust time was 14-24 h(mean,22.6 h).There were 1 case of postoperative absorption fever,2 cases of moderate anemia,and 2 cases of postoperative incision fat liquefaction.In the 2 patients with moderate anemia,one patient developed postoperative intramuscular artery rupture leading to massive bleeding and the formation of hematoma in the surgical area,with the amount of bleeding being approximately 1000 ml,and the other had moderate anemia before and after surgery.The hospital stay ranged 8-16 d(mean,11.6 d).Pathologic examinations showed high-grade uroepithelial carcer in all the patients.Postoperative follow-ups lasted 3-9 months,with a mean of 6.2 months.None had bladder tumor recurrence or distant metastasis.Conclusion Robot-assisted posterior laparoscopic modified"single-position"radical nephroureterectomy is safe and feasible.

Analysis of clinical presentation and genetic characteristics of malignant infantile osteopetrosis / 中华儿科杂志

Objective: To investigate the clinical presentation and genetic characteristics of malignant infantile osteopetrosis. Methods: This was a retrospective case study. Thirty-seven children with malignant infantile osteopetrosis admitted into Beijing Children's Hospital from January 2013 to September 2022 were enrolled in this study. According to the gene mutations, the patients were divided into the CLCN7 group and the TCIRG1 group. Clinical characteristics, laboratory tests, and prognosis were compared between two groups. Wilcoxon test or Fisher exact test were used in inter-group comparison. The survival rate was estimated with the Kaplan-Meier method and the Log-Rank test was used to compare the difference in survival between groups. Results: Among the 37 cases, there were 22 males and 15 females. The age of diagnosis was 0.5 (0.2, 1.0) year. There were 13 patients (35%) and 24 patients (65%) with mutations in CLCN7 and TCIRGI gene respectively. Patients in the CLCN7 group had an older age of diagnosis than those in the TCIRGI group (1.2 (0.4, 3.6) vs. 0.4 (0.2, 0.6) years, Z=-2.60, P=0.008). The levels of serum phosphorus (1.7 (1.3, 1.8) vs. 1.1 (0.8, 1.6) mmol/L, Z=-2.59, P=0.010), creatine kinase isoenzyme (CK-MB) (457 (143, 610) vs. 56 (37, 82) U/L, Z=-3.38, P=0.001) and the level of neutrophils (14.0 (9.9, 18.1) vs. 9.2 (6.7, 11.1) ×109/L, Z=-2.07, P=0.039) at diagnosis were higher in the CLCN7 group than that in the TCIRG1 group. However, the level of D-dimer in the CLCN7 group was lower than that in the TCIRGI group (2.7 (1.0, 3.1) vs. 6.3 (2.5, 9.7) μg/L, Z=2.83, P=0.005). After hematopoietic stem cell transplantation, there was no significant difference in 5-year overall survival rate between the two groups (92.3%±7.4% vs. 83.3%±7.6%, χ²=0.56, P=0.456). Conclusions: TCIRGI gene mutations are more common in children with osteopetrosis. Children with TCIRGI gene mutations have younger age, lower levels of phosphorus, CK-MB, and neutrophils and higher level of D-dimer at the onset. After hematopoietic stem cell transplantation, patients with CLCN7 or TCIRGI gene mutations have similar prognosis.

Anion photoelectron spectroscopy and density functional theory study of TM2Sin- (TM = V, Cr; n = 14-20) clusters.

We investigated the structural evolution and electronic properties of medium-sized silicon cluster anions doped with two transition metal atoms, TM2Sin- (TM = V, Cr; n = 14-20), by using mass-selective anion photoelectron spectroscopy combined with density functional theory (DFT) calculations. Putative ground state structures of these clusters were obtained by using a genetic algorithm coupled with the DFT calculations. It was found that the two TM atoms tend to form a TM-TM bond, which - except for V2Si19- - is shorter than the nearest neighbour distance in the crystalline state of the respective metals. The V2Sin- clusters with n = 14 to 17 exhibit structures based on a silicon hexagonal antiprism, while the larger ones exhibit more fullerene-like cage structures. Cr2Sin- clusters follow the same trend, although with a silicon hexagonal prism structure for n = 14 and 15, and the transition to fullerene-like structures occurring at n = 17. Among these clusters, TM2Si18- have the largest average binding energy and second order differences in energy, therefore the highest relative stability. All of the clusters possess total magnetic moment of 1 µB, but with very different contributions from the doped TM atoms. Especially in the Cr doped clusters there is a tendency towards an anitiferromagnetic arrangement of the magnetic moments of the two Cr atoms.

Structures and electronic properties of VSin- (n = 14-20) clusters: a combined experimental and density functional theory study.

We present a systematic study of the structures and electronic properties of vanadium-doped silicon cluster anions, VSin- (n = 14-20), by combining photoelectron spectroscopy (PES) measurements and density functional theory (DFT) based theoretical calculations. High resolution PES of low temperature (10 K) clusters are acquired at a photon wavelength of 248 nm. Low-lying structures of VSi14-20- are obtained by a genetic algorithm based global minimum search code combined with DFT calculations. Excellent agreement is found between the measured PES and the simulated electron density of states of the putative ground-state structures. We conclude that clusters with sizes n = 14 and n = 15 prefer cage-like structures, with the encapsulated vanadium atom bonding with all silicon atoms, while a fullerene-like motif is more favorable for n ≥ 16. For the sizes n = 16 to 19, the structures consist of a V@Si14 with two, three, four, and five Si atoms on the surface of the cage. For n = 20 the structure consists of a V@Si15 with five Si atoms on the surface of the cage. VSi14- has the highest stability and stands out as a simultaneous closing of electronic and geometrical shells.

Photoelectron Spectroscopy and Density Functional Investigation of the Structural Evolution, Electronic, and Magnetic Properties of CrSin- (n = 14-18) Clusters.

CrSin- (n = 14-18) cluster anions have been investigated by a combination of photoelectron spectroscopy (PES) and first-principles calculations. The lowest-lying structures of the clusters have been determined by a global minimum search based on the genetic algorithm, combined with density functional theory (DFT) calculations. The simulated PES spectra of the lowest-energy isomers are in agreement with the experimental results, which gives strong evidence that the correct structures have been found. While sizes n = 14 and n = 15 prefer cage-like structures based on multi-center bonding within the cage, the larger sizes adopt structures based on fullerene-type cages around the Cr atom, with the additional atoms attached to the cage surface. A Hirshfeld analysis shows that the Cr atoms act as electron donors in all clusters, thus enhancing the electron count in the cage. It also reveals that the magnetic moment of 1µB shown by all clusters is mainly contributed by the Cr atom. One interesting exception is size 17, where the Cr atom contributes a small moment antiparallel to that of the silicon cage.

Inhibitory effect of lidocaine on Kupffer cell inflammatory response and its effect on liver abscess formation in diabetic mice / 临床肝胆病杂志

Objective To investigate whether lidocaine can reverse Kupffer cell dysfunction in diabetic mice, as well as the mechanism of lidocaine in affecting liver abscess formation by improving the phagocytic function of Kupffer cells. Methods C57BLKS/J db/db mice were divided into diabetes control group and diabetes+lidocaine group, and C57BLKS/J db/m mice were divided into non-diabetes control group and non-diabetes+lidocaine group, with 5 mice in each group. All mice were fed with the suspension of Klebsiella pneumoniae . Kupffer cells were collected from each group and were cultured in vitro; an electron microscope was used to measure the change in ultrastructure, and Kupffer c ells were measured in terms of the levels of inflammatory mediators, the expression level of intercellular adhesion molecule-1 (ICAM-1), the chemotactic function of neutrophils, and phagocytic function; liver abscess formation was also observed. The Kruskal-Wallis H test was used for comparison of continuous data between multiple groups, and the Mann-Whitney U test was used for further comparison between two groups; the chi-square test was used for comparison of categorical data between groups. Results Compared with the non-diabetic mice, the diabetic mice had significant reductions in mitochondria and rough endoplasmic reticulum, endoplasmic reticulum dilation, mitochondrial swelling, and an increase in lipid droplets in Kupffer cells. Compared with the non-diabetes control group, the diabetes control group had significant increases in the levels of nitric oxide (NO) (4.95±0.06 μmol/L vs 1.34±0.13 μmol/L, P 0.05). Compared with the diabetes control group, the diabetes+lidocaine group had significant reductions in the levels of NO (3.35±0.28 μmol/L vs 4.95±0.06 μmol/L, P 0.05). Conclusion Lidocaine can inhibit Kupffer cell inflammatory response and improve the phagocytic function of Kupffer cells in diabetic mice, thereby exerting a protective effect on Kupffer cells, but it had no effect on liver abscess formation.

Research progress of micronucleus visualization analysis and artificial intelligence detection strategy / 中华预防医学杂志

The micronucleomics test can comprehensively display a variety of harmful endpoints, such as DNA damage and repair, chromosome breakage or loss and cell growth inhibition, with fast, simple and economical feature. Micronucleomics is not only widely used in the comprehensive assessment of the types and modes of genetic action of exogenous chemicals (such as drugs, food additives, cosmetics, environmental pollutants, etc.), but also plays an important role in the screening and risk assessment of cancer population at high risk. However, the traditional micronucleomics image counting method has the characteristics of time-consuming, low accuracy, and high cost, which cannot meet the current analysis requirements of large-scale, multi-index, rapidity, high precision and visualization. In recent years, with the rapid development of the era of precision medicine based on big data, visualized analysis of new micronucleomics based on machine learning and detection strategies based on deep learning have shown a good application prospect. This review, based on the application value of micronucleomics, systematically compares the traditional and new artificial intelligence counting of micronucleus images, and discusses the future direction of micronucleus image detection.

Effects of nano titanium dioxide on gut microbiota based on human digestive tract microecology simulation system in vitro / 北京大学学报(医学版)

OBJECTIVE@#To explore the effects of oral exposure to titanium dioxide nanoparticles (TiO2 NPs) on the composition and structure of human gut microbiota.@*METHODS@#The particle size, shape, crystal shape and degree of agglomeration in ultrapure water of TiO2 NPs were characterized. The in vitro human digestive tract microecological simulation system was established by simulating the fluid environment and physical conditions of stomach, small intestine and colon, and the stability of the simulation system was evaluated. The bacterial communities were extracted from human feces and cultured stably in the simulated system. They were exposed to 0, 20, 100 and 500 mg/L TiO2 NPs, respectively, and the bacterial fluids were collected after 24 h of exposure. The effect of TiO2 NPs on the composition and structure of human gut microbiota was analyzed by 16S rRNA sequencing technology. Linear discriminant analysis effect size (LEfSe) was used to screen differential bacteria, and the Kyoto encyclopedia of genes and genomes (KEGG) database for functional prediction.@*RESULTS@#The spherical and anatase TiO2 NPs were (25.12±5.64) nm in particle size, while in ultra-pure water hydrated particle size was (609.43±60.35) nm and Zeta potential was (-8.33±0.22) mV. The in vitro digestive tract microecology simulation system reached a relatively stable state after 24 hours, and the counts of Enterococci, Enterobacte-rium, and Lactobacillus reached (1.6±0.85)×107, (5.6±0.82)×107 and (2.7±1.32)×107, respectively. 16S rRNA sequencing results showed that compared with the control group, the number and evenness of gut microbiota were not significantly affected at phylum, class, order, family and genus levels in TiO2 NPs groups (20, 100 and 500 mg/L). The relative abundance of some species was significantly changed, and a total of 42 different bacteria were screened between the TiO2 NPs groups (20, 100 and 500 mg/L) and the control group [linear discriminant analysis(LDA) score>3], represented by Enterobacter, Bacteroidaceae, Lactobacillaceae, Bifidobacteriaceae and Clostridium. Further predictive analysis of gut microbiota function showed that TiO2 NPs might affect oxidative phosphorylation, energy meta-bolism, phosphonate and phosphonate metabolism, and methane metabolism (P < 0.05).@*CONCLUSION@#In human digestive tract microecological simulation system, TiO2 NPs could significantly change the composition and structure of human gut microbiota, represented by Enterobacter and probiotics, and may further affect a variety of metabolism and function of the body.

Prevalence and spatial distribution patterns of human echinococcosis at the township level in Sichuan Province, China.

BACKGROUND: Echinococcosis is a global zoonotic parasitic disease caused by Echinococcus larvae. This disease is highly endemic in Sichuan Province, China. This study investigates the prevalence and spatial distribution characteristics of human echinococcosis at the township level in Sichuan Province, geared towards providing a future reference for the development of precise prevention and control strategies. METHODS: Human prevalence of echinococcosis was evaluated using the B-ultrasonography diagnostic method in Sichuan Province between 2016 and 2019. All data were collected, collated, and analyzed. A spatial distribution map was drawn to intuitively analyze the spatial distribution features. Eventually, the spatial autocorrelation was specified and local indicators of spatial association (LISA) clustering map was drawn to investigate the spatial aggregation of echinococcosis at the township level in Sichuan Province. RESULTS: The prevalence of echinococcosis in humans of Sichuan Province was 0.462%, among which the occurrence of cystic echinococcosis (CE) was 0.221%, while that of alveolar echinococcosis (AE) was 0.244%. Based on the results of the spatial distribution map, a predominance of echinococcosis in humans decreased gradually from west to east and from north to south. The Global Moran's I index was 0.77 (Z = 32.07, P < 0.05), indicating that the prevalence of echinococcosis in humans was spatially clustered, exhibiting a significant spatial positive correlation. Further, the findings of local spatial autocorrelation analysis revealed that the "high-high" concentration areas were primarily located in some townships in the northwest of Sichuan Province. However, the "low-low" concentration areas were predominantly located in some townships in the southeast of Sichuan Province. CONCLUSIONS: Our findings demonstrated that the prevalence of echinococcosis in humans of Sichuan Province follows a downward trend, suggesting that the current prevention and control work has achieved substantial outcomes. Nevertheless, the prevalence in humans at the township level is widely distributed and differs significantly, with a clear clustering in space. Therefore, precise prevention and control strategies should be formulated for clusters, specifically strengthening the "high-high" clusters at the township level.

Low genetic variation in Echinococcus multilocularis from the Western Sichuan Plateau of China revealed by microsatellite and mitochondrial DNA markers.

The prevalence of E. multilocularis is a major public health problem in China. To better understand the molecular epidemiology and evolutionary patterns of E. multilocularis, an adequate dataset regarding the genetic variance of this parasite is necessary. However, for now, available genetic data of E. multilocularis is still insufficient. In the study, the EmsB microsatellite and the partial mitochondrial cox1 gene were combined to investigate the genetic diversity of 64 E. multilocularis samples from human, dogs and voles. These samples were collected in the Western Sichuan Plateau, where the highest village-based human prevalence of alveolar echinococcosis was recorded worldwide. The aim of the study is to gather more informative genetic data of E. multilocularis in the areas, especially those obtained using the EmsB marker. The microsatellite analysis revealed 7 different EmsB profiles, 1 of which was found in 90.63% of the total samples collected from all 3 hosts. This major profile was identical to the one detected in the same area 16 years ago. The rest of the 6 profiles, each represented by only 1 isolate, did not correspond to any of the profiles previously reported. All the profiles detected in the study belonged to the Asian cluster. Meanwhile, according to sequence analysis of the 758 bp cox1 region, 4 haplotypes all assigned to the Asian clade were detected among the isolates. A star-like haplotype network was exhibited with a centrally positioned haplotype found in 93.75% of the samples. The overall haplotype and nucleotide diversities were both low. These findings provided evidence for a founder event or bottleneck and subsequent population expansion in E. multilocularis. The EmsB profiles were not fully consistent with the cox1 haplotypes. The same correspondence relationship was mainly observed in samples with the major profile P5 and the main haplotype EmHa1. A total of 54 isolates assigned to profile P5 were classified to the EmHa1 haplotype. In conclusion, both the microsatellite and mtDNA markers showed low variability within the Tibetan population of E. multilocularis. An EmsB profile and a cox1 haplotype were found to be predominant in the study area, which appears to remain steady for over a decade. The results reinforce the higher potential of the microsatellite DNA marker with high discriminative power to identify the very low genetic polymorphism of E. multilocularis than that of the partial cox1 sequencing. The data obtained in the study would be helpful to enlarge the data pool to further probe the possible origins and dispersal of E. multilocularis in China.

Telomere length and telomerase: early biomarkers for environmental carcinogen exposure / 中国职业医学

Telomere is a DNA-protein complex located at the end of linear chromosome of eukaryotic cells, which has the function of stabilizing chromosome. The change of telomere length is closely related to the exposure to environmental carcinogens. The repair and elongation of telomere rely on the catalysis and mediation of telomerase. Exposure to typical environmental carcinogens polycyclic aromatic hydrocarbons(PAHs) can affect the change of telomere length by regulating the expression of telomere-related genes. Long-term exposure to PAHs can shorten the telomeres of peripheral blood leukocytes in a dose-response relationship. Telomere dysfunction is one of the important mechanisms of arsenic poisoning. The change of telomere length can be used as a biomarker of arsenic exposure. However, there are differences in the research results on the effect of arsenic exposure on telomere length, so the consistency of the effect of arsenic exposure on telomere length and the possible mechanism need to be further studied. Exposure to atmospheric fine particulate matter can attack genetic material by inducing oxidative stress and inflammatory response in the body, and then affect the telomere length of cells in vivo. Acute particulate matter exposure can increase telomere length in a short time(a few hours to a few days), and subsequent telomere shortening may be related to the inflammatory mechanism. Telomere length and telomerase activity can be used as biomarkers and play an important role in monitoring early carcinogenesis, diagnosis and prognosis assessment of cancers caused by environmental carcinogens.

Whole genome characteristics of four coxsackievirus A4 isolates associated with hand, foot and mouth disease / 中华微生物学和免疫学杂志

Objective:To investigate the whole genome characteristics of coxsackievirus A4 (CVA4) circulating in Qingdao city.Methods:Four CVA4 isolates circulating in Qingdao city during 2013 to 2015 were selected. Whole genome sequences of these strains were amplified by one-step reverse transcription-polymerase chain reaction (RT-PCR). Sequence alignment and phylogenetic analysis were performed using MEGA7.0 software package. Genetic recombination analysis was performed using similarity plots 3.5.1 software package.Results:Phylogenetic analysis showed that based on the sequences of the whole genome and P1, P2 and P3 regions, HS312/QD/CHN/2013 and HS605/QD/CHN/2014 strains together with the early domestic isolates belonged to the same clade, while FY218/QD/CHN/2015 strain and CV-A4/P1033/2013/China strain collected in Wenzhou in 2013 formed another clade in each phylogenetic tree. HS144/QD/CHN/2014 strain belonged to the same clade as HS312/QD/CHN/2014, HS605/QD/CHN/2014 and the early domestic CVA4 isolates in the phylogenetic tree based on the P1 region, but formed a separate clade in the phylogenetic trees based on the whole genome, P2 region and P3 region. Genetic recombination analysis revealed that there was genetic recombination between HS144/QD/CHN/2014 strain and the CVA2 strain of CV-A2/P373/2013/China isolated in mainland China in 2013 in the region of 2C-3D (5 081-7 301); FY218/QD/CHN/2015 and CV-A4/P1033/2013/China strains were highly homologous and recombination signal sequences were detected in the region of 2A-2B (3 821-4 161) between the two strains and the CVA2 strain of CV-A2/P373/2013/China.Conclusions:The CVA4 isolates circulating in Qingdao city presented obvious genetic diversity at the genome-wide level.

Risk of COVID-19 is associated with long-term exposure to air pollution

People with chronic obstructive pulmonary disease, cardiovascular disease or hypertension have a high risk of severe coronavirus disease 2019 (COVID-19). Long-term exposure to air pollution, especially PM2.5, has also been associated with COVID-19 mortality. We collated individual-level data of confirmed COVID-19 cases during the first wave of the epidemic in mainland China. We fitted a generalized linear model using city-level COVID-19 cases and severe cases as the outcome, and long-term average levels of air pollutants as the exposure. Our analysis was adjusted using several variables, including a mobile phone dataset, covering human movement from Wuhan before the travel ban and movements within each city during the time of emergency response. Other variables included census, smoking prevalence, climate, and socio-economic data from 324 cities in China. We adjusted for human mobility and socio-economic factors, and found that an increase in long-term NO2 or PM2.5 may correspond to an increase in the number of COVID-19 cases and severe infections. However, the linkage might also be affected by the confounding factor of population size because of the predefined correlation between population size and air pollution. The results are derived from a large, newly compiled and geocoded repository of population and epidemiological data relevant to COVID-19. The findings of this paper (and other previous studies that have given ambiguous results) indicate that a more definitive analysis is needed of the link between COVID-19 and air pollution.

Disease burden of echinococcosis in Tibetan communities-A significant public health issue in an underdeveloped region of western China.

Echinococcosis is considered by the World Health Organization (WHO) to be a neglected zoonotic disease in the world. Some Tibetan communities were found to be highly endemic for echinococcosis just 20 years ago. Until recently, we were able to understand the overall disease burden of echinococcosis in Tibetan communities after prevalence data being available from nationwide investigations from 2012 to 2016. Data were abstracted from 9 publications regarding to echinococcosis prevalence between 2016-2018; from 10 data bases on echinococcosis prevalence for 151 Tibetan counties; and statistics of population, Gross Domestic Product (GDP) and health staff from 44 local statistic bureaus and government websites at provincial, prefecture and county level, and 2 books of provincial yearly statistics. These data were used to estimate the Disability Adjusted Life Years (DALYs) due to cystic echinococcosis (CE) and alveolar echinococcosis (AE). The distribution of DALYs was presented geographically and economically. The echinococcosis DALYs in the Tibetan communities were estimated to be 126,159 (95%UI 122,415-137,675) annually using the method recommended by WHO. AE DALYs were estimated to be 105,829 (95%UI 101,969-117,090), which were more than CE DALYs of 20,330 (95%UI 19,690-21,581). Echinococcosis affects people more in underdeveloped areas. There was a tendency that a higher echinococcosis DALYs were usually correlated a higher altitude. Health services are also poorly provided in terms of number of health staff of 5.05 per 1000 population in comparison with the national average of 5.8 per 1000 population. The data suggest that the echinococcosis burden in the center region of Qinghai-Tibet plateau is higher than that of other regions, and consequently more control and health services should be provided to the region.

Effect of subchronic combined oral exposure of titanium dioxide nanoparticles and glucose on levels of serum folate and vitamin B12 in young SD rats / 北京大学学报(医学版)

OBJECTIVE@#To explore the effect of subchronic combined oral exposure of titanium dioxide nanoparticles and glucose on levels of serum folate and vitamin B12 in young SD rats.@*METHODS@#At first, the physical and chemical properties of titanium dioxide nanoparticles, such as particle size, shape, crystal form and agglomeration degree in solution system, were characterized in detail. Eighty 4-week-old young SD rats were randomly divided into 8 groups (10 rats in each group, half male and half female). The rats were exposed to titanium dioxide nanoparticles through intragastric administration at 0, 2, 10 and 50 mg/kg body weight with or without 1.8 g/kg glucose daily for 90 days. At last, the concentrations of serum folate and vitamin B12 were detected.@*RESULTS@#Titanium dioxide nanoparticles were anatase crystals, closely spherical shape, with an average particle size of (24±5) nm. In male young rats, compared with the control group, the serum folate concentration was significantly increased when exposed to titanium dioxide nanoparticles (10 mg/kg) and glucose. The difference was statistically significant (P<0.05). However, in female and male young rats, compared with glucose (1.8 g/kg) exposure group, titanium dioxide nanoparticles (50 mg/kg) and glucose significantly reduced the serum folate concentration. The difference was statistically significant (P<0.05). Through statistical analysis of factorial design and calculation of interaction, obvious antagonistic effect was observed between titanium dioxide nanoparticles and glucose on the serum folate concentration in the young female SD rats. The combined oral exposure of titanium dioxide nanoparticles and glucose had little effect on the concentration of serum vitamin B12 in the young SD rats, with no significant interaction between the two substances. It was only found that titanium dioxide nanoparticles (2 mg/kg) and glucose significantly increased the serum vitamin B12 concentration, compared with glucose (1.8 g/kg) exposure group. The difference was statistically significant (P<0.05).@*CONCLUSION@#Subchronic combined oral exposure of titanium dioxide nanoparticles and glucose had an obvious antagonistic effect on serum folate concentrations in young SD rats.

Effects of titanium dioxide nanoparticles on fecal metabolome in rats after oral administration for 90 days / 北京大学学报(医学版)

OBJECTIVE@#To explore the effects and related mechanisms of oral exposure titanium dioxide nanoparticles (TiO2 NPs) for 90 days on the intestinal and the gut microbiota of rats, through fecal metabolomics.@*METHODS@#Twelve 4-week-old clean-grade Sprague Dawley (SD) rats were randomly de-vided into 2 groups by body weight, treated with TiO2 NPs at dose of 0 or 50 mg/kg body weight everyday respectively for 90 days. The solution of each infection was freshly prepared and shocked fully by ultrasonic. Characterization of the particle size, crystal form, purity, and specific surface area of TiO2 NPs was conducted. And the fresh feces of the rats were collected on the 90th day. After lyophilized and hydrophilic phase extraction, ultra performance liquid chromatography-Q-exactive orbitrap-high-resolution mass spectrometry system (UPLC-QEMS) was utilized for non-targeted determination of fecal meta-bolites. The metabolites were identified and labeled through Compound Discoverer 3.0 software, and used for subsequent metabolomics analysis. Bioinformatics analysis was carried out including unsupervised principal component analysis and supervised orthogonal projection to latent structure discriminant analysis for the differential metabolites between the two groups. The differential metabolites were followed-up for Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis.@*RESULTS@#Compared with the control group, the body weight of the rats was significantly reduced (P<0.05) in the treatment group. A total of 22 metabolites in fecal metabolomics showed significant changes. Among them, xanthine, 1-methyladenine, 3-hydroxypyridine, methionine sulfoxide, pyridoxine, 1,5-isoquinolinediol, N-acetylornithine, N-acetyl-D-galactosamine, L-citrulline, L-methionine, leucine, DL-tryptophan, L-ornithine, 4-methyl-5-thiazoleethanol, and L-glutamic acid totaled 15 metabolites increased significantly. N-acetylhistamine, D-pipecolinic acid, imidazolelactic acid, L-valine, 2,3,4,6-tetramethylpyrazine, caprolactam, and histamine totaled 7 metabolites decreased significantly. N-acetylhistamine, L-valine and methionine sulfoxide were changed more than 16 times. Analysis of KEGG pathway revealed that the two metabolic pathways arginine biosynthesis and aminoacyl-tRNA biosynthesis were significantly changed (false discover rate < 0.05, pathway impact > 0.1).@*CONCLUSION@#Oral exposure to TiO2 NPs for 90 days could disrupt the metabolism of the intestine and gut microbiota, causing significant changes in metabolites and metabolic pathways which were related to inflammatory response, oxidative stress, glucose homeostasis, blood system and amino acid homeostasis in rat feces. It is suggested that the toxic effect of TiO2 NPs on rats may be closely related to intestinal and gut microbiota metabolism.

Influence of oxidative/antioxidative biomarkers and inflammatory cytokines on rats after sub-acute orally administration of titanium dioxide nanoparticles / 北京大学学报(医学版)

OBJECTIVE@#To evaluate the sub-acute oral effect of titanium dioxide (TiO2) nanoparticles on the oxidation/antioxidation biomarkers and inflammatory cytokines in blood, liver, intestine, and colon in rats.@*METHODS@#Twenty four 4-week-old clean-grade Sprague Dawley (SD) rats were randomly devided into 4 groups by body weight (n=6, control, low, middle, and high), in which the rats were orally exposed to TiO2 nanoparticles at doses of 0, 2, 10 and 50 mg/kg body weight/day for 28 consecutive days separately. Food intake, body weight and abnormal behaviors during the experiment were recorded. The rats were euthanized on the 29th day. The blood was collected via abdominal aortic method and centrifuged to collect the serum. Tissues from liver, intestine and colon were collected and homogenated. Then enzyme-linked immunosorbent assay (ELISA) and microwell plate methods were used to detect oxidation/antioxidation biomarkers including superoxide dismutase (SOD), glutathione (GSH), glutathione peroxidase (GSH-Px), total mercapto (T-SH), glutathione disulfide (GSSG), malomdialdehvde (MDA) and inflammatory cytokines including interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) in the serum, liver, intestine and colon in the rats.@*RESULTS@#Compared with the control group, no significant differences in body weight, food intake and organ coefficients were observed in all the three groups after TiO2 gavage. No significant changes in GSH, GSH-Px, T-SH, and IL-6 were observed. Compared with the control group, significant increase of SOD activity in serum in high dose group, signi-ficant increase of GSSG concentration in intestine in middle and high dose group and significant increase of MDA concentration in liver in low and high dose group were observed. Compared with the control group, a significant increase of TNF-α in liver in middle and high dose group was observed.@*CONCLUSION@#TiO2 nanoparticle can increase antioxidant enzymes activities in blood, increase oxidative biomarkers in liver and intestine, increase inflammatory cytokines in liver in rats after a 28-day sub-acute orally administration. Among blood, liver, intestine, and colon, liver is most sensitive to the toxicity induced by TiO2 nanoparticles, followed by intestine, blood, and colon in sequence.

Screening serum biomarkers for occupational exposure to titanium dioxide nanoparticles using metabolomics / 中国职业医学

OBJECTIVE: To screen the serum biomarkers in workers occupationally exposed to titanium dioxide nanoparticles(TiO_2 NPs) using metabolomics technology. METHODS: Using a typical sampling method, 56 workers who have occupationally exposed to TiO_(2 )in a TiO_2 NPs manufacturer were selected as the exposure group and 44 employees without occupational exposure to TiO_2 were selected as the control group. The high performance liquid chromatography-mass spectrometry technology was used to perform non-targeted metabolomics detection. The difference in serum metabolite profiles of the TiO_2 NPs exposure group and the control group were analyzed. Key differential metabolites and potential biomarkers were screened. The sensitivity and specificity of biomarkers were assessed through receiver operating characteristic(ROC) curve.RESULTS: We detected a total of 1 492 mass spectrum peaks in serum samples by serum metabolomics analysis, and 413 well-matched metabolites were obtained after annotation and identification. The results of principal component analysis and orthogonal partial least squares discriminant analysis showed that a total of 296 differentially expressed metabolites were found in the serum of individuals of the exposure group compared with the control group(all P<0.01). Among them the relative expression of metabolites increased in 265 species and decreased in 31 species. The ROC analysis results showed that the area under the ROC curve of five metabolites exceeded 0.900, and these metabolites included tanacetol A,(5 E)-2-hydroxy-4-oxobenzopenta-5-en-1-ylacetic acid, triterpene saponins organic compounds, 9,10,13-trihydroxystearic acid, and liquoric acid. The multiple linear regression analysis showed that the relative expression of all the five metabolites were positively correlated with occupational exposure to TiO_2 NPs after adjusting for the influence of confounding factors such as gender, age, body mass index, smoking and drinking(all P<0.01). CONCLUSION: Occupational exposure to TiO_2 NPs could induce changes in serum metabolite profiles. The metabolites represented by tanacetol A in serum can be used as potential biomarkers for indicating occupational exposure to TiO_2 NPs.