[Hg Content Characteristics and Safe Planting Zoning of Paddy Soil and Rice in Guizhou Province].

Guizhou Province ranks first in terms of Hg reserves and production in the country, and rice is its largest grain crop. In order to study the characteristics and pollution causes of soil-rice Hg content at the provincial level in Guizhou and to carry out safe planting zoning, 1 564 pairs of soil-rice samples, 470 natural soil samples, and 203 individual paddy soil samples were collected to test their Hg content and basic physical and chemical properties of the soil. The results showed that:① Paddy soil was mainly neutral and acidic, the paddy soil ω (Hg) range was 0.005-93.06 mg·kg-1, and the geometric mean was 0.864 mg·kg-1. The Hg content of paddy soil in Guizhou Province was significantly higher than that in natural soil (0.16 mg·kg-1,P < 0.05). Compared with the filtered value and control value, the soil samples exceeded the standard by 63.25% and 14.71%, respectively. Among them, the soil Hg pollution in Danzhai County of Qiandongnan Prefecture, Wuchuan County of Zunyi City, Zhenfeng County of Qianxinan Prefecture, and Wanshan District of Tongren City was more prominent. ② Rice ω(Hg) ranged from 0.000 5 to 0.52 mg·kg-1, and the geometric mean was 0.010 mg·kg-1, the percentage of rice Hg content exceeding the standard was 25.87%, and the exceeding points were mainly distributed in Suiyang County of Zunyi City, Zhenfeng County of Qianxinan Prefecture, Xixiu District of Anshun City, Bijiang District of Tongren City, and other industrial and mining activity-intensive areas. ③ The majority of the study area was in the priority protection category (74.75%); the safe use category accounted for (24.62%); and the strictly controlled category (0.93%) was scattered in Danzhai County at the border between Qiannan Prefecture and Qiandongnan Prefecture, Zhenfeng County in Qianxinan Prefecture, and Wanshan District in Tongren. It is not recommended to plant rice, which can be used as feed for reproduction.

Research progress of traditional Chinese medicine monomer and compound intervention on the Wnt signaling pathway in regulating bone metabolism / 中国药房

Bone metabolism refers to the decomposition and anabolism occurring during bone remodeling， and its balance is regulated by bone resorption and bone formation. A slight deviation of this balance causes various skeletal diseases， such as osteoporosis and renal osteodystrophy. Traditional Chinese medicine （TCM） monomers and compounds have certain advantages in treating bone metabolism diseases. The Wnt signaling pathway includes the canonical Wnt signaling pathway， dependent on β-catenin， and the non-canonical Wnt signaling pathway， independent of β-catenin. Both types of pathways can maintain bone metabolism balance by regulating bone formation and bone resorption and are essential for bone development， bone mass maintenance， and bone remodeling. A variety of TCM monomers （albiflorin， catalpol and icariin） and formulas （Zuogui pill， Yishen gugu prescription， Duzhong jiangu prescription， etc.） have been confirmed to promote differentiation of bone marrow mesenchymal stem cells， proliferation and differentiation of osteoblasts， bone injury repair， and osteoporosis improvement by activating the Wnt signaling pathway in recent years. Here， this article summarizes the research progress in the Wnt signaling pathway regulation of bone metabolism by TCM monomers and compounds to provide ideas for the clinical application of TCM and the research and development of new drugs for the prevention and treatment of bone metabolism diseases.

Correlation between Combined Urinary Metal Exposure and Grip Strength under Three Statistical Models: A Cross-sectional Study in Rural Guangxi / 生物医学与环境科学（英文）

OBJECTIVE@#This study aimed to investigate the potential relationship between urinary metals copper (Cu), arsenic (As), strontium (Sr), barium (Ba), iron (Fe), lead (Pb) and manganese (Mn) and grip strength.@*METHODS@#We used linear regression models, quantile g-computation and Bayesian kernel machine regression (BKMR) to assess the relationship between metals and grip strength.@*RESULTS@#In the multimetal linear regression, Cu (β = -2.119), As (β = -1.318), Sr (β = -2.480), Ba (β = 0.781), Fe (β = 1.130) and Mn (β = -0.404) were significantly correlated with grip strength ( P < 0.05). The results of the quantile g-computation showed that the risk of occurrence of grip strength reduction was -1.007 (95% confidence interval: -1.362, -0.652; P < 0.001) when each quartile of the mixture of the seven metals was increased. Bayesian kernel function regression model analysis showed that mixtures of the seven metals had a negative overall effect on grip strength, with Cu, As and Sr being negatively associated with grip strength levels. In the total population, potential interactions were observed between As and Mn and between Cu and Mn ( P interactions of 0.003 and 0.018, respectively).@*CONCLUSION@#In summary, this study suggests that combined exposure to metal mixtures is negatively associated with grip strength. Cu, Sr and As were negatively correlated with grip strength levels, and there were potential interactions between As and Mn and between Cu and Mn.

Study on the Role and Mechanism of METTL3 Mediating the Up-regulation of m6A Modified Long Non-coding RNA THAP7-AS1 in Promoting the Occurrence of Lung Cancer / 中国肺癌杂志

BACKGROUND@#Lung cancer is a major threat to human health. The molecular mechanisms related to the occurrence and development of lung cancer are complex and poorly known. Exploring molecular markers related to the development of lung cancer is helpful to improve the effect of early diagnosis and treatment. Long non-coding RNA (lncRNA) THAP7-AS1 is known to be highly expressed in gastric cancer, but has been less studied in other cancers. The aim of the study is to explore the role and mechanism of methyltransferase-like 3 (METTL3) mediated up-regulation of N6-methyladenosine (m6A) modified lncRNA THAP7-AS1 expression in promoting the development of lung cancer.@*METHODS@#Samples of 120 lung cancer and corresponding paracancerous tissues were collected. LncRNA microarrays were used to analyze differentially expressed lncRNAs. THAP7-AS1 levels were detected in lung cancer, adjacent normal tissues and lung cancer cell lines by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The diagnostic value of THAP7-AS1 in lung cancer and the relationship between THAP7-AS1 expression and survival rate and clinicopathological parameters were analyzed. Bioinformatics analysis, methylated RNA immunoprecipitation (meRIP), RNA pull-down and RNA-immunoprecipitation (RIP) assay were used to investigate the molecular regulation mechanism of THAP7-AS1. Cell proliferation, migration, invasion and tumorigenesis of SPC-A-1 and NCI-H1299 cells were determined by MTS, colony-formation, scratch, Transwell and xenotransplantation in vivo, respectively. Expression levels of phosphoinositide 3-kinase/protein kenase B (PI3K/AKT) signal pathway related protein were detected by Western blot.@*RESULTS@#Expression levels of THAP7-AS1 were higher in lung cancer tissues and cell lines (P<0.05). THAP7-AS1 has certain diagnostic value in lung cancer [area under the curve (AUC)=0.737], and its expression associated with overall survival rate, tumor size, tumor-node-metastasis (TNM) stage and lymph node metastasis (P<0.05). METTL3-mediated m6A modification enhanced THAP7-AS1 expression. The cell proliferation, migration, invasion and the volume and mass of transplanted tumor were all higher in the THAP7-AS1 group compared with the NC group and sh-NC group of SPC-A-1 and NCI-H1299 cells, while the cell proliferation, migration and invasion were lower in the sh-THAP7-AS1 group (P<0.05). THAP7-AS1 binds specifically to Cullin 4B (CUL4B). The cell proliferation, migration, invasion, and expression levels of phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA), phosphoinositide-3 kinase, catalytic subunit delta (PIK3CD), phospho-phosphatidylinositol 3-kinase (p-PI3K), phospho-protein kinase B (p-AKT) and phospho-mammalian target of rapamycin (p-mTOR) were higher in the THAP7-AS1 group compared with the Vector group of SPC-A-1 and NCI-H1299 cells (P<0.05).@*CONCLUSIONS@#LncRNA THAP7-AS1 is stably expressed through m6A modification mediated by METTL3, and combines with CUL4B to activate PI3K/AKT signal pathway, which promotes the occurrence and development of lung cancer.

Non-canonical function of histone methyltransferase G9a in the translational regulation of chronic inflammation.

We report a novel translation-regulatory function of G9a, a histone methyltransferase and well-understood transcriptional repressor, in promoting hyperinflammation and lymphopenia; two hallmarks of endotoxin tolerance (ET)-associated chronic inflammatory complications. Using multiple approaches, we demonstrate that G9a interacts with multiple translation regulators during ET, particularly the N6-methyladenosine (m6A) RNA methyltransferase METTL3, to co-upregulate expression of certain m6A-modified mRNAs that encode immune-checkpoint and anti-inflammatory proteins. Mechanistically, G9a promotes m6A methyltransferase activity of METTL3 at translational/post-translational level by regulating its expression, its methylation, and its cytosolic localization during ET. Additionally, from a broader view extended from the G9a-METTL3-m6A translation regulatory axis, our translatome proteomics approach identified numerous "G9a-translated" proteins that unite the networks associated with inflammation dysregulation, T cell dysfunction, and systemic cytokine response. In sum, we identified a previously unrecognized function of G9a in protein-specific translation that can be leveraged to treat ET-related chronic inflammatory diseases.

[Low Accumulation Characteristics of Sweet-waxy Maize in Pb and Cd Complex Contaminated Soils Based on Field Trials].

To screen out sweet-waxy maize varieties with low accumulation characteristics suitable for planting in lead (Pb) and cadmium (Cd) complex contaminated soils, 39 maize varieties were selected, and the enrichment characteristics and differences of grains and straws on Pb and Cd were studied through field trials. Maize yield, bioaccumulation factors, and soil Pb and Cd risk thresholds were used as evaluation indicators for screening low accumulation maize varieties. The results showed that there were significant differences between the yield and Pb and Cd contents in grains and straws of different varieties of maize (P<0.05). Bioaccumulation factors of grains for Pb and Cd were in the range of 0.00003-0.00230 and 0.01-0.15, respectively, and those of straws for Pb and Cd were in the range of 0.003-0.065 and 0.64-4.28, respectively. Through the cluster analysis of bioaccumulation factors, the soil Pb and Cd risk thresholds of different varieties of maize were comprehensively obtained:Huitian 5, Xinmeitian 818, and Yunuo 9 could be safely produced in the farmland with Pb and Cd content exceeding the risk control value, and Tianguinuo 937 and Jinwannuo 2000 could be safely produced in the farmland with Cd content exceeding the risk screening value. Huitian 5, Xinmeitian 818, and Yunuo 9, as low Pb and Cd accumulation varieties, were suitable to be popularized on Pb and Cd polluted soil in Guangxi, China. Tianguinuo 937 and Jinwannuo 2000, as low grain and high Cd accumulation varieties, are suggested to be used as phytoremediation resources.

Missense Mutation in Human CHD4 Causes Ventricular Noncompaction by Repressing ADAMTS1.

BACKGROUND: Left ventricular noncompaction (LVNC) is a prevalent cardiomyopathy associated with excessive trabeculation and thin compact myocardium. Patients with LVNC are vulnerable to cardiac dysfunction and at high risk of sudden death. Although sporadic and inherited mutations in cardiac genes are implicated in LVNC, understanding of the mechanisms responsible for human LVNC is limited. METHODS: We screened the complete exome sequence database of the Pediatrics Cardiac Genomics Consortium and identified a cohort with a de novo CHD4 (chromodomain helicase DNA-binding protein 4) proband, CHD4M202I, with congenital heart defects. We engineered a humanized mouse model of CHD4M202I (mouse CHD4M195I). Histological analysis, immunohistochemistry, flow cytometry, transmission electron microscopy, and echocardiography were used to analyze cardiac anatomy and function. Ex vivo culture, immunopurification coupled with mass spectrometry, transcriptional profiling, and chromatin immunoprecipitation were performed to deduce the mechanism of CHD4M195I-mediated ventricular wall defects. RESULTS: CHD4M195I/M195I mice developed biventricular hypertrabeculation and noncompaction and died at birth. Proliferation of cardiomyocytes was significantly increased in CHD4M195I hearts, and the excessive trabeculation was associated with accumulation of ECM (extracellular matrix) proteins and a reduction of ADAMTS1 (ADAM metallopeptidase with thrombospondin type 1 motif 1), an ECM protease. We rescued the hyperproliferation and hypertrabeculation defects in CHD4M195I hearts by administration of ADAMTS1. Mechanistically, the CHD4M195I protein showed augmented affinity to endocardial BRG1 (SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily A, member 4). This enhanced affinity resulted in the failure of derepression of Adamts1 transcription such that ADAMTS1-mediated trabeculation termination was impaired. CONCLUSIONS: Our study reveals how a single mutation in the chromatin remodeler CHD4, in mice or humans, modulates ventricular chamber maturation and that cardiac defects associated with the missense mutation CHD4M195I can be attenuated by the administration of ADAMTS1.

STING Suppresses Mitochondrial VDAC2 to Govern RCC Growth Independent of Innate Immunity.

STING is an innate immune sensor for immune surveillance of viral/bacterial infection and maintenance of an immune-friendly microenvironment to prevent tumorigenesis. However, if and how STING exerts innate immunity-independent function remains elusive. Here, the authors report that STING expression is increased in renal cell carcinoma (RCC) patients and governs tumor growth through non-canonical innate immune signaling involving mitochondrial ROS maintenance and calcium homeostasis. Mitochondrial voltage-dependent anion channel VDAC2 is identified as a new STING binding partner. STING depletion potentiates VDAC2/GRP75-mediated MERC (mitochondria-ER contact) formation to increase mitochondrial ROS/calcium levels, impairs mitochondria function, and suppresses mTORC1/S6K signaling leading to RCC growth retardation. STING interaction with VDAC2 occurs through STING-C88/C91 palmitoylation and inhibiting STING palmitoyl-transferases ZDHHCs by 2-BP significantly impedes RCC cell growth alone or in combination with sorafenib. Together, these studies reveal an innate immunity-independent function of STING in regulating mitochondrial function and growth in RCC, providing a rationale to target the STING/VDAC2 interaction in treating RCC.

HSP90ß chaperoning SMURF1-mediated LATS proteasomal degradation in the regulation of bone formation.

Heat shock protein 90 (HSP90) molecular chaperone is responsible for the stabilization and biological activity of a diverse set of client proteins. We have previously demonstrated that inhibition of HSP90 by 17-Demethoxy-17-allyaminogeldanmycin (17-AAG) not only reverses the glucocorticoid-induced bone loss but also enhances the basal level of bone mass in mice. Here, we investigate the potential mechanism underlying HSP90-associated osteoblast differentiation and bone formation. Knockdown of HSP90ß but not HSP90α or inhibition of HSP90 by 17-AAG or NVP-BEP800 negates the protein levels of large tumor suppressor (LATS), the core kinases of Hippo signaling, resulting in the inactivation of LATS and activation of Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ), in the enhancement of osteoblastic differentiation. In contrast, genetic ablation of Lats1 in mesenchymal stem cells is sufficient to abolish the HSP90 inhibition-induced osteoblastic differentiation and bone formation. Mechanistically, HSP90ß but not HSP90α chaperones and prevents the SMAD specific E3 ubiquitin protein ligase 1 (SMURF1)-mediated and ubiquitination-dependent LATS protein proteasomal degradation, whereas 17-AAG abolishes these effects of HSP90ß. Thus, these results uncover the HSP90ß chaperoning SMURF1-mediated LATS protein proteasomal degradation and the subsequent YAP/TAZ activation as a hitherto uncharacterized mechanism controlling osteoblastic differentiation and bone formation.

Serum Anti-Fumarate Hydratase Autoantibody as a Biomarker for Predicting Prognosis of Acute-on-Chronic Liver Failure

Background/Aims@#To investigate the autoantibody against fumarate hydratase (FH), which is a specific liver failure-associated antigen (LFAA) and determine whether it can be used as a biomarker to evaluate the prognosis of acute-on-chronic liver failure (ACLF). @*Methods@#An immunoproteomic approach was applied to screen specific LFAAs related to differential prognosis of ACLF (n=60). Enzyme-linked immunosorbent assay (ELISA) technology was employed for the validation of the frequency and titer of autoantibodies against FH in ACLF patients with different prognoses (n=82). Moreover, we clarified the expression of autoantibodies against FH in patients with chronic hepatitis B (n=60) and hepatitis B virus-related liver cirrhosis (n=60). The dynamic changes in the titers of autoantibodies against FH were analyzed by sample collection at multiple time points during the clinical course of eight ACLF patients with different prognoses. @*Results@#Ultimately, 15 LFAAs were screened and identified by the immunoproteomic approach.Based on ELISA-based verification, anti-FH/Fumarate hydratase protein autoantibody was chosen to verify its expression in ACLF patients. ACLF patients had a much higher anti-FH autoantibody frequency (76.8%) than patients with liver cirrhosis (10%, p=0.000), patients with chronic hepatitis B (6.7%, p=0.022), and normal humans (0%, p=0.000). More importantly, the frequency and titer of anti-FH protein autoantibodies in the serum of ACLF patients with a good prognosis were much higher than that of patients with a poor prognosis (83.9% vs 61.5%, p=0.019; 1.41±0.85 vs 0.94±0.56, p=0.017, respectively). The titer of anti-FH autoantibodies showed dynamic changes in the clinical course of ACLF. @*Conclusions@#The anti-FH autoantibody in serum may be a potential biomarker for predicting the prognosis of ACLF.

Left Ventricle Longitudinal Strain Parameters Are Effective for Differentiating Cardiac Amyloidosis from Primary Hypertensive Left Ventricular Hypertrophy / 中山大学学报(医学科学版)

ObjectiveTo clarify the value of the left ventricular longitudinal strain（LVLS）parameters in patients with cardiac amyloidosis （CA） and primary hypertension with left ventricular hypertrophy （HLVH）. MethodsForty-one patients confirmed with CA were selected and assigned to CA with hypertension group （n =14） and pure CA group （n=27） based on the initial diagnosis with or without hypertension. Twenty patients with primary hypertension-induced left ventricular hypertrophy （HLVH group） and twenty healthy controls were also selected， matching for gender， age， and body surface area. Clinical data， conventional echocardiography parameters were collected and LVLS parameters were measured. Within-group variations were compared among the four groups， and pairwise comparisons were conducted between groups. The sensitivity and specificity of each parameter in predicting CA were judged by the receiver operator characteristic （ROC） curvy in CA and HLVH patients with left ventricular ejection fraction （LVEF） preserved. ResultsAmong the conventional echocardiography parameters， LVEF and left ventricular end-diastolic diameter （LVEDD） were lower in the CA with hypertension group and pure CA group compared with the higher values in the HLVH group and control group. Whereas， left ventricular posterior wall thickness （LVPWT）， relative wall thickness （RWT）， and average E/e' were higher in the two CA groups compared with the HLVH group （all P＜0.05）.Among the LVLS parameters， Global longitudinal strain （GLS） was the worst in the CA with hypertension group so as pure CA group， modest in the HLVH group， and highest in the control group. On the contrary， relative longitudinal strain and ejection fraction strain ratio （EFSR） were the highest in the CA with hypertension group so as to pure CA group， modest in the HLVH group， and lowest in the control group （all P＜0.05）. ROC analysis showed that when LVEF was preserved， the absolute value of GLS less than 14.35% and EFSR higher than 4.28 could effectively distinguish CA from HLVH （all AUCs＞0.9，all P＜0.05）； meanwhile GLS showed high sensitivity（100%） and EFSR showed great specificity（95%）. There were not statistically significance in any parameter between CA with hypertension group and pure CA group（all P＞0.05）. ConclusionWhether CA was complicated with hypertension or not， there were statistically significance among routine echocardiography and LVLS parameters compared with HLVH. In particular， GLS and EFSR are accurate in predicting CA in patients with myocardial hypertrophy and preserved LVEF.

Artificial intelligence cell image analysis technology can improve the accuracy of bone marrow cells / 中华检验医学杂志

Objective:To evaluate the screening efficacy of AI for bone marrow cell morphology.Method:Bone marrow specimens of patients attending the Second Hospital of Hebei Medical University from December 1,2019 to December 21,2020;(1) Selected from one hundred bone marrow specimens, The cases included chronic myeloid cell leukemia ( n=23), myelodysplastic syndrome ( n=4), chronic lymphocytic leukemia ( n=4), multiple myeloma ( n=5), 7 acute leukemia ( n=7), chronic anemia ( n=32), infection ( n=6) and healthy control ( n=15). Including 45 males and 55 females, with age 52(37,66)years old.The bone marrow smear prepared with Wright-Giemsa, The AI analysis system and manual audit were applied to classify 13 types of bone marrow nucleated cell, taking the results of manual audit as the gold standard, comparing the difference between the results of the two methods, using statistical software to draw the confusion matrix, The compliance between the manual audit results and the pre-classification results of the AI analysis system was calculated by the Kappa consistency test method; The consistency analysis between the pre-classification results of AI and those of the manual microscopic examination was performed by the Pearson test; (2)Statistics analyzed the blast cell differential count differences of AI and manual microscopy, to evaluate the clinical application value of AI analysis system, which soured from thirty bone marrow samples of patients diagnosed with MDS and AML. Results:76 630 images of 13 nucleated cells were obtained by AI analysis system; the weighted average experimental diagnostic efficiency parameters of 13 types of bone marrow nucleated cells, are as follows: sensitivity(%)=95.82, specificity(%)=99.19, accuracy(%)=98.89, false positive rate(%)=0.81, false negative rate (%)=4.18; the correlation results, between the pre-classification results of AI and manual microscopic classification results,showed that blast cell, promyelocytes, neutrophilic myelocyte, neutrophilic metamyelocyte, band neutrophil, segmented neutrophi,eosinophil, basophil, polychromatic erythroblast, orthochromatic erythroblast, and lymphocytes have good positive correlation ( r>0.70,all P<0.001), while basophilic erythroblast and monocytes have no obvious correlation ( r=0.32,0.30, all P> 0.001); the count results of the blast cells in bone marrow smears of MDS and AML, got by AI and manual microscopy respectively, showed that the average percentage of blast cells was 8.19% by AI and 8.68% by manual microscopy in MDS, there was no significant difference between the two methods ( P>0.05); the average percentage of blast cells was 48.52% by AI analysis system and 53.77% by manual microscopy in AML, and although there was a significant difference in blast cell count ( P<0.01), coincidence the classification diagnostic criteria for AML (blast cells ≥ 20%). Conclusion:The AI analysis system performed good sensitivity, specificity and accuracy for 13 types of bone marrow nucleated cells, which showed potential application value for the rapid classification and diagnosis of MDS and AML.

Implementation and influencing factors analysis of nursing evidence of perioperative deep vein thrombosis prevention for patients with brain neoplasms based on the Ottawa model of research use / 中国实用护理杂志

Objective:To evaluate the clinical status, and analyz obstacles and facilitators for perioperative deep vein thrombosis prevention of brain neoplasms based on the Ottawa model of research use (OMRU).Methods:A total of 93 patients with brain tumors who were admitted to the Department of Neurosurgery, the First Affiliated Hospital of Nanjing Medical University from April to May 2021 and 33 nurses in the neurosurgery ward and operating room neurosurgery special group were selected as the baseline review subjects by convenience sampling. Based on the framework of evidence-based continued quality improvement of Fudan University, we searched BMJ Best Practice, UpToDate, The Joanna Briggs Institute Library, International Guideline Library, American Guideline Network, Scottish Intercollegiate Guideline Network, National Institutes for Health and Clinical Technology Optimization, Medline, Medlive, China National Knowledge Infrastructure, VIP, Wanfang and SinoMed according to the '6S' evidence pyramid from inception to January 1, 2021 for all clinical decisions, recommended practices, best practice information, evidence summary, guidelines and expert consensus on venous thrombosis assessment, prevention, screening, nursing and health education. The best evidence was summarized, and the final review indicators were formulated through two rounds of expert correspondence. According to the results of baseline review, barriers and facilitators were analyzed, and countermeasures were developed guided by OMRU.Results:A total of 19 best evidences were included, and 34 review indicators were developed in this study. Among them, only 4 indicators had a compliance rate of 100%, 18 ones had a compliance rate of 0, and the other 12 ones had a compliance rate of 6.5%-97.8%. A multi-factor analysis of the review results showed that the main obstacles of evidence implementation were the feasibility and comprehensibility at evidence level, the lack of knowledge and heavy workloads at the potential practitioner level, insufficient education materials, trainings and preventive equipment at system level. Furthermore, the reliable sources of evidence at evidence level, supports from practitioners at the potential practitioner level and system resources (such as training, national and hospital policies, etc.) at system level may contribute to the clinical application of evidence.Conclusions:There was still a huge gap between the best evidence and clinical practice. The obstacles and facilitating factors in evidence transformation should be evaluated scientifically and comprehensively, and corresponding countermeasures should be given to promote the application of evidence in clinical practice.

Safety and immunogenicity of freeze-dried rabies vaccine (Vero-cells) for human use in healthy people aged 9-65 years / 中华预防医学杂志

Objective: To assess the safety and immunogenicity of freeze-dried rabies vaccine (Vero-cells) for human use on different immunization procedures in healthy people aged 9-65 years. Methods: A randomized, blind, positive-controlled clinical study was conducted in March 2015. The eligible residents aged 9-65 were recruited in Dengfeng city and Biyang County, Henan Province. A total of 1 956 subjects were enrolled. The subjects were randomly (1∶1∶1) assigned to 5-dose control group, 4-dose trial group and 5-dose trial group, with 652 subjects in each group. The subjects of 5-dose control group were immunized with control vaccine on days 0, 3, 7, 14 and 28. The subjects of 4-dose trial group were immunized with trial vaccine on days 0, 7 and 21 (2-1-1 phases) and the subjects of 5-dose trial group were immunized with trial vaccine on days 0, 3, 7, 14 and 28. A combination of regular follow-up and active reporting was used to observe local and systemic adverse reactions till 30 days after the first and full immunization, and the incidence rate of adverse reactions in three groups was analyzed and compared. The venous blood was collected before the first immunization, 7 days after the first immunization, 14 days after the first immunization and 14 days after the full immunization. The neutralizing antibody of rabies virus was detected by rapid fluorescent focus inhibition test (RFFIT), and the seropositive conversion rate and geometric mean concentration (GMC) of antibody were calculated. Results: The adverse reaction rates in 5-dose control group, 4-dose trial group and 5-dose trial group were 41.87% (273/652), 35.43% (231/652) and 34.97% (228/652), respectively. The adverse reaction rates of 4-dose trial group and 5-dose trial group were lower than those of the 5-dose control group (P<0.05). The local reactions were mainly pain, itching, swelling and redness in injection site, while the systemic reactions were mainly fever, fatigue, headache and muscle pain. The severity of adverse reactions was mainly mild (level 1), accounting for 85.33% (518/607), 89.02% (373/419) and 88.96% (427/480) of the total number of adverse reactions in each group. At 14 days after the first immunization and 14 days after the full immunization, the antibody positive conversion rates of three groups were all 100%. At 7 days, 14 days after the first immunization and 14 days after the full immunization, the GMCs of three groups were 0.60, 0.72, 0.59 IU/ml, 20.42, 23.99, 24.38 IU/ml and 22.95, 23.52, 24.72 IU/ml, respectively, with no significant difference (P>0.05). Conclusion: The freeze-dried rabies vaccine (Vero-cells) for human use has good safety and immunogenicity when inoculated according to 5-dose and 4-dose immunization procedures.

Research progress of microparticles in traditional Chinese medicine decoction / 药学学报

Decoction is a classical dosage form of traditional Chinese medicines. In the process of decocting, various complex components produce physical interactions and chemical reactions, among which physical interactions include van der Waals force, hydrogen bond, electrostatic interaction, π-π stacking, etc., and chemical reactions include Maillard reaction, oxidation reaction, hydrolysis reaction, degradation reaction, polymerization reaction, etc. New substances and original ingredients from chemical reactions can be further activated. These effects form the basis of particle formation in the broth. The sizes of the particles in decoctions range from nanoscale to micron scale, mostly composed of polysaccharide, protein matrix, wrapped in water insoluble molecules, can increase the dispersion of insoluble components and the stability of unstable components, as well as reduce the volatile components and toxic components of volatile components, and ultimately achieve the purpose of efficient absorption and toxicity reduction. From the angle of physical change and chemical reaction in the process of decoction, this paper expounds the formation mechanism of particles in decoction, expounds the research method of particles, analyzes the components in particles and the interaction between components, and then explains the pharmacodynamic characteristics of traditional Chinese medicine decoction, which provides the foundation for the modernization of Chinese decoction.

The Ubiquitin Ligase SMURF1 Catalyzes the Polyubiquitination of ADAR1 / 中国生物化学与分子生物学报

It is known that SMAD specific E3 ubiquitin protein ligase 1 (SMURF1) mediates autophagy through its E3 ubiquitin ligase activity, but the ubiquitinated substrates of SMURF1 need to be further explored. In this paper, the interacting proteins of SMURF1 in THP-1 cells were captured and identified by co-immunoprecipitation (Co-IP) combined with mass spectrometry. It was found that SMURF1 could physically bind to 222 proteins in THP-1 cells, and Adenosine deaminase acting on RNA 1 (ADAR1) had a higher peptide binding score. SMURF1 overexpression vectors were constructed and transfected into HEK-293T cells, then Co-IP and Western blotting assays verified the interaction between exogenous SMURF1 and endogenous ADAR1. qRT-PCR and Western blotting assays were carried out after transfecting SMURF1 overexpression vectors in HEK-293T cells, which identified that overexpression of SMURF1 attenuated the protein levels of ADAR1 (P<0. 05). However, there was no significant difference in the mRNA level of ADAR1. HEK-293T cells with normal and overexpressing SMURF1 were treated with cycloheximide (CHX), respectively, and Western blotting assays showed a shortened half-life of ADAR1 after overexpression of SMURF1 (P < 0. 05). Furthermore, overexpression of SMURF1 increased the polyubiquitination level of ADAR1 as detected by Co-IP and Western blot (P<0. 05). After the proteasome inhibitor (MG132) treatment, the Western blotting assay was performed to demonstrate that the negative regulatory effect of SMURF1 on ADAR1 was weakened after the proteasome degradation pathway was attenuated (P<0. 05). This study shows that SMURF1 interacts with ADAR1, catalyzes the polyubiquitination of ADAR1 and mediates its degradation through the proteasome pathway, which provides a theoretical basis for exploring the various biological functions of SMURF1 by affecting the stability of ADAR1.