Objective To investigate the changes of serum metabolites in patients with occupational chronic lead poisoning using non-targeted metabolomics, and to screen differential metabolic pathways. Methods A total of 14 patients with occupational chronic lead poisoning were selected as the poisoning group, and 14 healthy people without occupational hazard exposure history were selected as the control group using the judgment sampling method. Serum of the individuals from the two groups was collected. Non-targeted metabolomics technology based on ultra high performance liquid chromatography-tandem mass spectrometry was used to detect serum metabolite levels in the two groups. Differential metabolites (DMs) were screened by the principal component analysis, partial least squares discriminant analysis and orthogonal partial least squares discriminant analysis, and related metabolic pathways were explored. Results The blood lead level in the poisoning group was higher than that in the control group (median: 359.59 vs 5.04 μg/L, P<0.01). There were significant differences in serum metabolites between the poisoning group and control group. After the combination of results from the positive and negative ion patterns, a total of 89 DMs were screened in serum of patients in the poisoning group, including 50 upregulated and 39 downregulated metabolites compared with the control group. The serum DMs of poisoning group were mainly enriched in arginine biosynthesis, ABC transporter, purine metabolism, choline metabolism in malignant tumor, glycerophospholipid metabolism and ether lipid metabolism compared with the control group (all P<0.05). Conclusion Abnormal changes of serum metabolic profile occurred in patients with occupational chronic lead poisoning. The metabolic pathways such as arginine biosynthesis, ABC transporter, purine metabolism, choline metabolism, glycerophospholipid metabolism and ether lipid metabolism may be involved in the occurrence and development of lead poisoning.

Acute respiratory infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had caused a global pandemic since 2019, and posed a serious threat to global health security. Traditional Chinese medicine (TCM) has played an indispensable role in the battle against the epidemic. Many components originated from TCMs were found to inhibit the production of SARS-CoV-2 3C-like protease (3CLpro) and papain-like protease (PLpro), which are two promising therapeutic targets to inhibit SARS-CoV-2. This study describes a systematic investigation of the roots and rhizomes of Sophora tonkinensis, which results in the characterization of 12 new flavonoids, including seven prenylated flavanones (1-7), one prenylated flavonol (8), two prenylated chalcones (9-10), one isoflavanone (11), and one isoflavan dimer (12), together with 43 known compounds (13-55). Their structures including the absolute configurations were elucidated by comprehensive analysis of MS, 1D and 2D NMR data, and time-dependent density functional theory electronic circular dichroism (TDDFT ECD) calculations. Compounds 12 and 51 exhibited inhibitory effects against SARS-CoV-2 3CLpro with IC₅₀ values of 34.89 and 19.88 μmol·L^-1, repectively while compounds 9, 43 and 47 exhibited inhibitory effects against PLpro with IC₅₀ values of 32.67, 79.38, and 16.74 μmol·L^-1, respectively.
Flavonoids/chemistry* ; SARS-CoV-2 ; Rhizome ; COVID-19 ; Peptide Hydrolases ; Antiviral Agents/chemistry*

BACKGROUND: This study aimed to evaluate the correlation between long non-coding RNA (lncRNA)-related single nucleotide polymorphisms (SNPs) and susceptibility to silicosis. METHODS: First, RNA-sequencing (RNA-seq) data were comprehensively analyzed in the peripheral blood lymphocytes of eight participants (four silicosis cases and four healthy controls) exposed to silica dust to identify differentially expressed lncRNAs (DE-lncRNAs). The functional SNPs in the identified DE-lncRNAs were then identified using several databases. Finally, the association between functional SNPs and susceptibility to silicosis was evaluated by a two-stage case-control study. The SNPs of 155 silicosis cases and 141 healthy silica-exposed controls were screened by genome-wide association study (GWAS), and the candidate SNPs of 194 silicosis cases and 235 healthy silica-exposed controls were validated by genotyping using the improved Mutiligase Detection Reaction (iMLDR) system. RESULTS: A total of 76 DE-lncRNAs were identified by RNA-seq data analysis (cut-offs: fold change > 2 or fold change < 0.5, P < 0.05), while 127 functional SNPs among those 76 DE-lncRNAs were identified through multiple public databases. Furthermore, five SNPs were found to be significantly correlated with the risk of silicosis by GWAS screening (P < 0.05), while the results of GWAS and iMLDR validation indicated that the variant A allele of rs1814521 was associated with a reduced risk of silicosis (OR = 0.76, 95% CI = 0.62-0.94, P = 0.011). CONCLUSION The presence of the SNP rs1814521 in the lncRNA ADGRG3 is associated with susceptibility to silicosis. Moreover, ADGRG3 was found to be lowly expressed in silicosis cases. The underlying biological mechanisms by which lncRNA ADGRG3 and rs1814521 regulate the development of silicosis need further study.
Case-Control Studies ; Genetic Predisposition to Disease ; Genome-Wide Association Study ; Humans ; Polymorphism, Single Nucleotide ; RNA, Long Noncoding/genetics* ; Silicosis/genetics*

Objective:To evaluate the performance, efficacy and safety of a novel portable endoscopy system for upper gastrointestinal examination.Methods:A multicentered, open-label, randomized, non-inferiority controlled study was conducted in 3 clinical research centers from June 2019 to June 2020, and a total of 90 outpatients admitted to Department of Gastroenterology were randomly assigned to the trial group ( n=44) undergoing portable endoscopy and the control group ( n=46) undergoing Olympus endoscopy. The examination success rate, image quality, performance, overall operation satisfaction rate, biopsy success rate and adverse events of the two groups were compared. Results:The examination success rates of the trial group and the control group were 97.73% (43/44) and 100.00% (46/46) respectively with a difference of -2.27% (95% CI: -6.68%-2.13%), higher than the set non-inferiority margin of -10%. Rates of good and excellent image quality were 100% in both groups, and the difference of 0 was higher than the set non-inferiority margin of -10%. There was no significant difference in the rate of good and excellent performance of the operating system between the two groups [97.67% (42/43) VS 100.00% (46/46), P=0.483]. There was significant difference in the overall satisfactory rate of the operation between the two groups [86.05% (37/43) VS 100.00% (46/46), P=0.011]. A total of 9 cases underwent endoscopic biopsy, including 5 cases in the trial group and 4 cases in the control group. The biopsy channels in both groups were smooth and the biopsy were successfully completed. There was no significant difference in adverse event rate between the two groups [25.00% (11/44) VS 10.87%(5/46), χ2=3.07, P=0.080]. All adverse events disappeared in 48 hours, and no severe adverse events or device defect events occurred. Conclusion:The novel portable endoscopic system is comparable to Olympus endoscopic system in terms of the operating performance, the image quality and safety. Therefore, this system is safe and effective for upper gastrointestinal examination.

Objective: This paper studies the nutritional and vision health status of Tibetan migrant students and the differences between the local students in Lanzhou and them to provide a theoretical basis for nutrition intervention and vision protection for students. Methods: Cluster sampling method was used to select 2 434 students migrating from Gannan Tibetan Autonomous Prefecture to a boarding middle school, and 3 291 students from three middle schools in Qilihe District of Lanzhou from September to December 2020. All the students were administered physical and visual examination. Proportion of nutritional status, poor eyesight and myopia by gender and age groups between Tibetan migrant students and local students were analyzed. Results: The detection rate of overweight and obesity in Tibetan migrant boys(2.8%,5.7%) and girls(11.0%,8.3%) was lower than that of local students of the same sex(5.6%,8.3%;24.9%,20.9%) ( χ 2=12.17,7.21, P <0.05; χ 2=81.33,91.34, P <0.05); The detection rate of malnutrition in Tibetan migrant boys(9.9%) was higher than that in local boys(7.2%) ( χ 2=6.65, P <0.05). The detection rate of poor vision in Tibetan migrant boys was lower than that in local boys ( χ 2=3.93, P <0.05). The detection rate of myopia was significantly lower than that of local students ( χ 2=975.82, P <0.01). The detection rate of abnormal color vision in Tibetan migrant boys was higher than that in local boys ( χ 2=8.38, P <0.05). The detection rate of abnormal color vision in Tibetan migrant girls was lower than that in local girls ( χ 2=8.08, P <0.05). The detection rate of mild and moderate visual impairment was lower among Tibetan migrant boys than local boys ( χ 2=3.88, 8.32, P <0.05); the detection rate of mild, moderate and severe myopia was lower than local boys ( χ 2= 13.72 ,55.96, 338.50, P <0.05). The detection rate of mild, moderate and severe myopia was lower among Tibetan migrant girls than local girls ( χ 2=7.62, 37.79,424.00, P <0.05). Conclusion Tibetan migrant students was lower than that of local students. More attention should be paid to nutrition intake of Tibetan boys to prevent malnutrition. The detection rate of myopia in Tibetan migrant students is low,but the detection rate of severe poor vision among Tibetan students in the junior high school group is higher than that of local students, and attention should be paid to the visual health of Tibetan students in junior high school.

Objective:To explore whether the regular feedback system in opportunistic screening of colorectal cancer can improve the adenoma detection rate (ADR) of endoscopists.Methods:This study was an observational study, divided into three stages: the baseline stage before intervention (the pre-intervention period), the regular feedback stage (the intervention period) and the post-intervention stage (the post-intervention period). In the pre-intervention period, all patients who underwent opportunistic screening of colorectal cancer in Department of Gastroenterology in Beijing Shijitan Hospital Affiliated to Capital Medical University from June 2017 to May 2018 were reviewed, and the ADR of each endoscopist was calculated. In the intervention period from June 2018 to November 2018, colonoscopies were performed on patients for opportunistic screening of colorectal cancer by endoscopists who participated in the feedback. The ADR of each endoscopist during the previous month was calculated at the beginning of each month and feedback was provided in the form of a report. In the post-intervention period from December 2018 to January 2019, colonoscopies were performed on patients for opportunistic screening of colorectal cancer by endoscopists who participated in the feedback. The ADR of each endoscopist was calculated after the feedback stopped. ADR and polyp detection rate (PDR) of three stages were compared.Results:A total of 1 768, 1 308 and 344 patients were enrolled for opportunistic screening of colorectal cancer during the pre-intervention, the intervention and the post-intervention period respectively. Eight endoscopists participated in the whole process of this study. The total ADR increased from 23.70% (419/1 768) in the pre-intervention period to 33.72% (441/1 308) in the intervention period ( χ2=37.449, P<0.05). Two months after intervention, ADR decreased slightly to 33.14% (114/344), but was still higher compared with before ( χ2=13.602, P<0.05). The total PDR increased from 47.17% (834/1 768) in the pre-intervention period to 52.68% (689/1 308) in the intervention period ( χ2=9.111, P<0.05). Two months after the intervention, PDR increased slightly to 53.78% (185/344), and still higher compared with before ( χ2=5.035, P<0.05). Conclusion:Regular feedback to endoscopists can improve ADR in opportunistic screening of colorectal cancer.

OBJECTIVE：To simultaneo usly determine the contents of atractylenolide Ⅱ ，β-eudesmol，atractyloxin and atractylone in Atractylodes chinensis ，and to evaluate the quality of A. chinensis with different growth years combined with color difference principle. METHODS ：HPLC method was adopted. The determination performed on Agilent Eclipse XDB-C 18 column with mobile phase consisted of acetonitrile- 0.2％ phosphoric acid （gradient elution ）at the flow rate of 1.0 mL/min；the detection wavelengths were set as 208 nm（atractylenolide Ⅱ，β-eudesmol），340 nm（atractyloxin）and 220 nm（atractylone）；the sample size was 15 μ L. Using atractyloxin as reference，QAMS was adopted to establish relative correction factors （RCFs） of atractylenolideⅡ，β-eudesmol and atractylone ；the content of each component in A. chinensis with different growth years were calculated. The contents of above 4 components were determined by external standard method and then compared with the results of QAMS. The color difference values of A. chinensis powder were measured based on color difference principle. The correlation analysis of above 4 components content with color was carried out by Pearson correlation analysis. RESULTS ：The separation degree of atractylenolide Ⅱ，β-eudesmol，atractyloxin and atractylone in A. chinensis was higher than 1.5. The linear range were 1.01-10.10，3.30-33.00，4.40-44.00，5.34-53.40 μg/mL，respectively. RSDs of precision ，reproducibility and stability tests were all lower than 2％，while the average recovery rates were 101.34％-104.67％（RSD＜1.5％，n＝6）. Using atractyloxin as reference ， RCFs of atractylenolide Ⅱ，β-eudesmol and atractylone were 3.896 7，5.928 2，9.727 9，with RSD of 0.35％，2.89％，0.36％ （n＝6），respectively. Relative deviation of 3 components （except for atractyloxin ） in 24 batches of A. chinensis ranged 0.03％-1.45％ between QAMS and external standard method ，which indicated that the results of two methods were consistent ，and the content of each component increased with the increase of growth years. Atractylenolide Ⅱ，β-eudesmol，atractyloxin and atractylone in A. chinensis had significant negative correlation with its color shade （L*），total color difference （E*ab）（P＜0.01）， and significant positive correlation with color red-green direction （a*）， color yellow-blue direction （b*）（P＜0.01）. CONCLUSIONS：The established HPLC-QAMS method can be used for the determination of atractylenolide Ⅱ，β-eudesmol， atractyloxin and atractylone in A. chinensis . The longer the growth period is ，the higher each component content is. The color of A. chinensis is closely related to the content of each component ，and the content of effective components is higher in A. chinensis with dark yellowish brown color.

An information service model of subject librarians was proposed according to the semantic-linked data, changing retrieval methods of ontology technology users, and ontology.This model provides an open application in-terface by making use of SOA for the semantic-based information service, establishes the expanded semantic-linked relation between resources by constructing the driving engine and knowledge database based on linked data technolo-gy, and builds subject librarian platform, medical expert platform and subject user platform.Subject librarians can thus provide intelligent information retrieval service for medical users at semantic level under the help of medical experts.

BACKGROUND:Hepatocyte transplantation has attracted more and more attention as a therapeutic measure for liver failure and genetic metabolic liver diseases.OBJECTIVE:TO evaluate the efficacy and safety of human hepatocyte transplantation in treating hepatitis B related liver failure in one case by a 2-year follow-up.DESIGN:A case-report of 2-year follow-up.SETTING:No.9 Department of Infectious Diseases,Bioengineering Research Room,the 302 Hospital of Chinese PLA.PARTICI PANT:One inpatient with hepatitis B related liver failure was selected from the 302 Hospital of Chinese PLA.and she was diagnosed according the laboratory tests.The transplanted hepatocytes were originated frOm the healthy liver of a 24-year-old man,who had signed the protocol for liver donation before death.METHODS:The hepatocyte transplantation was completed in the Department of Radiology,the 302 Hospital of Chinese PLA in December 2004.Liver was isolated to obtain human primary hepatocytes, and then cryopreserved.The hepatocytes were transplanted into recipient spleen via femoral vein after resuscitation.The clinical symptoms,changes of blood biochemical indexes,and changes of spleen MRI signals were observed before and after operation.The patient was reexamined every half a year after operation, including liver function, blood coagulation function,B-mode ultrasonography,gastroscopy and MRI,and she was followed up for 2 years. MAIN OUTCOME MEASURES:Liver function,blood coagulation function, imaging indexes, immunological indexes,complication and rejection.RESULTS:①Totally(1-2)×1010 hepatocytes were harvested,and the viability of rewarmed hepatocytes was 60%,and finally 2×109 hepatocytes were transplanted.②Two months later,the clinical symptoms of the recipient were obviously ameliorated,and serum bilirubin and aspartate aminotransferase(AST)were obviously decreased,while prothrombin activity was markedly increased.20 months later,the MRI results showed that there was hepatocyte image in spleen.Two years after operation.the total bilirubin level was 20 μmol/L,direct bilirubin level was 7 μmol/L, alanine aminotransferase was 416.75 nkat/L,AST was 533.44 nkat/L,albumin was 37 g/L,prothrombin activity was 90%,which were all obviously ameliorated as compared with those before operation(474.5 μmol/L,340.3 μmol/L,400.08 nkat/L,1 200.24 nkat/L,38 g/L,25%).The patient left the hospital 2 months later and could do light-burdened job.No complications of hydroperitonia and liver function failure, etc.were observed,and no rejection occurred.Several reexaminations by B-mode ultrasonography all indicated the further aggravations of liver cirrhosis and esophageal varices.She was admitted to hospital for twice because of esophageal varices bleeding,and cured by endoscopic variceal sclerosis therapy.CONCLUSION:Hepatocyte transplantation can ameliorate liver function without rejection,but it cannot relieve portal hypertension.

Objective To study the changes in PAF and its receptor in Kupffer cells in experimental cirrhosis and to evaluate the role of activated Kupffer cells in portal hypertension. Methods Kupffer cells, isolated from the livers of control and CCl_4-induced cirrhotic rats, were cultured in serum-free medium overnight. PAF synthesis and release by Kupffer cells were determined 24 h later by rapid ~3H-PAF scintillation proximity assay, and the expression of PAF receptor in Kupffer cells by saturation binding technique and semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR). By immunohistochemisty, the distribution of PAF in Kupffer cells was surveyed. Results Cell-associated PAF synthesis and release was increased about 1.48 fold and 2 fold, respectively, by Kupffer cells in cirrhotic liver as compared with the control (P0.05). Consistent with the receptor binding capacity, the mRNA expression of PAF receptor increased significantly in the Kupffer cells of cirrhotic liver (P