Objective To investigate the pollution status of main indoors air pollution factor, CO and CO2, in Guangzhou City, and to study the feasibility of using same standards in pollution monitoring. Methods 822 sampling points of various public places were monitored. Public places were classified into 1 group (≤5 mg/m3)?2 group(≤10 mg/m3)?3 group(CO level was not require to monitor)by CO level and were classified into Ⅰgroup(≤0.07%)?Ⅱgroup(≤0.10%)?Ⅲgroup(≤0.15%) by CO2 level. The 822 statistics of various public places were analyzed according to the standard value of hygienic Standard for Public Place. Results The results of the monitoring value of CO and CO2 showed as positive bias distribution. Average of CO was (2.76?1.41)mg/m3, the 95% percentile was 6.2 mg/m3; CO2 average value was (0.060?0.020)%, the 95% percentile was 0.099%. There was no significant difference among CO concentrations in 3 public places classified according to the standard (?2=3.70, P=0.157), but significant difference had been seen among CO2 (?2=35.266, P

Objective To explore a method with good repeatibility, less interference factors and easily controllable experimental conditions for evaluating the filtering efficiency of air filters Methods This evaluating method referred to Standard Examination Method of Household Portable Electrically Powered Air Purifying Set of America(ANSI/AHAM Ac 1 1998) and used the index of the frequency of air filtration (TAF) in the determination.The required sampling space volumes and the sampling duration of testing were determined based on the related different of air capacities.The levels of CO,CO 2,inhalable particulate(IP),NO 2,SO 2 and total count of air bacteria in filtered air were determined Results IP and total count of air bacteria could be used as sensitive indexes for evaluating the efficiency of air filtration Conclusion This method avoided many interference factors.It presented shorter duration of examination,good repeatibility and stability,easy operation and acturally reflected the efficiency of air filters

ObjectiveTo systematically review the effects of bilingual training on cognition for older adults. MethodsResearches about bilingual training for cognition for the older adults were retrieved from PubMed, Web of Science, ScienceDirect, SpringerLink, Wanfang Data, and CNKI from 2011 to May, 2021, supplemented by references backtracking and manual retrieval. The data was extracted for analysis. ResultsA total of 21 researches were included from twelve countries, which published mainly on journals of medicine, neurology, psychology, biology, etc., in 2017 and 2019. Most of the researches were prospective researches and retrospective researches, and the targeted groups including healthy people, people with dementia and people with Alzheimer's disease (AD). The objects mainly involved the effects of bilingualism on cognition, the pathways and the limitations. ConclusionBilingual training may improve the cognition for older adults, through the brain connection related with memory, attention and execution, to delay the onset of AD or dementia; which may associate with the improvement of brain structure and function, including connectivity among regions, activation of cortical circuits, and structural integrity and plasticity. The effects are mainly on execution and perception, and delaying the cognitive decline, which appear in a short term. Bilingual training may finally promote language function, maintain the integrity of the brain structures, and compensate cognitive decline using more potential neural circuits. However, these researches need more uniform criteria for subjects, more reasonable control conditions, and more uniform paradigms.

【Objective】 To explore the relationship between the methylation level of CNR1 and autism spectrum disorder (ASD), in order to provide a theoretical basis for the etiology of ASD. 【Methods】 A case-control study was conducted, recruiting 30 children with ASD from the Child Development and Behavior Research Center of Harbin Medical University and a rehabilitation facility, and 30 matched typically developed children from June 2017 to December 2018. The methylation levels of CNR1 in peripheral blood were measured by the Agena MassArray^® Mass Spectrometry System. A univariate conditional Logistic regression model was used to analyze the potential association between the methylation level of CNR1 and the risk of ASD with adjustment for age, BMI, body fat percentage and body fat. The correlations between the methylation level of CNR1 and the score of Social Responsiveness Scale (SRS) were evaluated by Pearson/Spearman correlation analysis. 【Results】 The methylation levels of the average methylation (t=2.224), CpG_3.4 (Z=2.187), CpG_9.10.11 (t=2.308), and CpG_28.29 (t=2.943) of the CNR1 promoter region in ASD children were significantly higher than controls (P<0.05). The methylation levels of the average methylation (OR=1.117, 95%CI: 1.003 - 1.245), CpG_9.10.11 (OR= 1.072, 95%CI:1.006 - 1.142), and CpG_28.29 (OR=1.078, 95%CI: 1.018 - 1.141) of the CNR1 promoter region were positively correlated with the risk of ASD (P<0.05). The methylation level of CpG_28.29 in ASD children was positively correlated with the scores of social motivation in SRS (r=0.421, P<0.05). 【Conclusions】 The methylation levels of CNR1 in peripheral blood are abnormal in ASD children and might be correlated with the risk of ASD and social function. The underlying mechanism needs to be further explored.

ObjectiveTo investigate the predictive indicators of early efficacy of Bushen Shengxue prescription combined with western medicine in the treatment of aplastic anemia， and provide prognosis indicators for the treatment of aplastic anemia （AA） with kidney-tonifying therapy in traditional Chinese medicine （TCM） combined with western medicine. MethodA total of 126 patients treated by Bushen Shengxue prescription combined with western medicine in 19 hospitals including Xiyuan Hospital of the China Academy of Chinese Medical Sciences from September 2018 to March 2021 were selected for a retrospective study. The therapy was proven to be effective after six months of treatment. According to the efficacy after 4 months of treatment， the patients were assigned into a 4-month effective group and a 4-month ineffective group. The age， sex， disease severity （including severe aplastic anemia and non-severe aplastic anemia）， course of disease， degree of bone marrow nucleated cell proliferation， baseline hemogram levels ［including white blood cell count （WBC）， absolute neutrophil count （ANC）， hemoglobin （HGB）， platelets （PLT）， and reticulocytes （RET）］， T lymphocytes subsets， and the expression levels of T-box transcription factor （T-bet） and GATA-binding protein-3 （GATA-3） were compared between the two groups before treatment. ResultThe proportions of patients within the age ranges of ［20， 40） and ［60， 80） were higher in the 4-month effective group （P<0.05）. The sex， disease severity， course of disease， and comorbidities had no significant differences between the two groups. The 4-month effective group had higher baseline levels of HGB， WBC， ANC， and PLT than the 4-month ineffective group （P<0.05）， and there was no significant difference in the RET level between the two groups before treatment. Binary Logistic regression analysis showed that the PLT level before treatment was an independent factor affecting the onset time， while other indicators did not affect the onset time. The receiver operating characteristic （ROC） curve was established to analyze the value of PLT level before treatment for predicting the onset time， and the area under the curve was 0.691. With the critical value of 40.5×10⁹/L， the sensitivity and specificity of the prediction that the therapy will take effect within 4 months were 0.569 and 0.893， respectively. The two groups of patients were graded according to age ｛（14， 20）， ［20， 40）， ［40， 60）， and ［60， 80）｝ and PLT level before treatment （PLT<40×10⁹/L， PLT≥40×10⁹/L）. The proportion of the patients with PLT≥40×10⁹/L before treatment in the 4-month effective group was significantly higher than that in the 4-month ineffective group （P<0.05）. The degree of bone marrow nucleated cell proliferation before treatment had no significant difference between the two groups. The level of total T lymphocytes in the 4-month effective patients was lower than that in the 4-month ineffective patients before treatment （P<0.05）. The levels of Th1 cells， Th2 cells， CD4⁺ T cells， and CD8⁺ T cells showed no significant differences between the two groups before treatment. The T-bet expression level in the 4-month effective group was higher than that in the 4-month ineffective group before treatment （P<0.05）， while the expression level of GATA-3 showed no significant difference between the two groups before treatment. ConclusionBushen Shengxue prescription combined with western medicine will achieve faster effect for the patients within the age ranges of ［20， 40） or ［40， 60）， with higher levels of HGB， WBC， ANC， and PLT （especially those with PLT≥40×10⁹/L）， lower level of total T lymphocytes， or higher T-bet expression level before treatment.

ObjectiveTo investigate the efficacy of Bushen Shengxue prescription and Yiqi Yangxue prescription in the treatment of chronic aplastic anemia and the effect on T cell subsets and the expression of T-box expressed in T cells （T-bet） and GATA binding protein 3 （GATA3）. MethodA total of 585 patients with chronic aplastic anemia who were treated in 19 hospitals in China from May 2018 to June 2021 were enrolled. With the prospective， double-blind and randomized control methods， the patients were randomized into three groups： kidney deficiency group， Qi and blood deficiency group， and control group. The three groups were respectively treated with Bushen Shengxue prescription granule， Yiqi Yangxue prescription granule， and Placebo （half the dose of Bushen Shengxue formula granules）. In addition， all of them were given oral cyclosporin and androgen. The treatment lasted 6 months， with 3 months as a course. The blood routine indexes， T cell subsets， and fusion genes T-bet and GATA3 before and after treatment were analyzed， and the safety indexes were monitored. ResultDuring the observation， a total of 75 cases dropped out and 18 were rejected. Finally， 161 cases in the kidney deficiency group， 164 in the Qi and blood deficiency group， and 167 in the control group were included. After 6 months of treatment， the total effective rate was 98.8% （159/161） in the kidney deficiency group， which was higher than the 79.9% （131/164） in the Qi and blood deficiency group （χ²=30.135， P<0.01） and the 61.7% （103/167） in the control group （χ²=70.126， P<0.01）. The total effective rate was higher in the Qi and blood deficiency group than in the control group （χ²=13.232， P<0.01）. After treatment， the hemoglobin （HGB） content increased significantly in three groups （P<0.05） as compared with that before treatment， particularly the kidney deficiency group （P<0.01）. After treatment， the white blood cell （WBC） count and platelet （PLT） count in the kidney deficiency group and the control group increased compared with those in the Qi and blood deficiency group （P<0.01）. There was no specific difference in neutrophils （ANC） after treatment among the three groups. At the same time point， the level of T helper type 1 （Th1） cells， Th1/Th2 ratio （P<0.05）， level of CD4⁺， and CD4⁺/CD8⁺ ratio （P<0.05） were significantly low in the kidney deficiency group among three groups. There was no significant difference in CD19^-， HLA/DR⁺， and CD25⁺ between the kidney deficiency group and the other two groups， but the T-bet of the kidney deficiency group and the control group was lower than that of the Qi and blood deficiency group （P<0.05）. ConclusionBushen Shengxue prescription exerts therapeutic effect on the aplastic anemia by improving the immunoregulatory mechanism， inhibiting the activity of immune system， modulating T cell subsets， suppressing Th1 and CD4⁺， and promoting bone marrow hematopoiesis. Moreover， it is safe with little side effects， which is worthy of further promotion.

Aging-induced changes in the immune system are associated with a higher incidence of infection and vaccination failure. Lymph nodes, which filter the lymph to identify and fight infections, play a central role in this process. However, careful characterization of the impact of aging on lymph nodes and associated autoimmune diseases is lacking. We combined single-cell RNA sequencing (scRNA-seq) with flow cytometry to delineate the immune cell atlas of cervical draining lymph nodes (CDLNs) of both young and old mice with or without experimental autoimmune uveitis (EAU). We found extensive and complicated changes in the cellular constituents of CDLNs during aging. When confronted with autoimmune challenges, old mice developed milder EAU compared to young mice. Within this EAU process, we highlighted that the pathogenicity of T helper 17 cells (Th17) was dampened, as shown by reduced GM-CSF secretion in old mice. The mitigated secretion of GM-CSF contributed to alleviation of IL-23 secretion by antigen-presenting cells (APCs) and may, in turn, weaken APCs' effects on facilitating the pathogenicity of Th17 cells. Meanwhile, our study further unveiled that aging downregulated GM-CSF secretion through reducing both the transcript and protein levels of IL-23R in Th17 cells from CDLNs. Overall, aging altered immune cell responses, especially through toning down Th17 cells, counteracting EAU challenge in old mice.
Aging ; Animals ; Autoimmune Diseases ; Disease Models, Animal ; Granulocyte-Macrophage Colony-Stimulating Factor/metabolism* ; Mice ; Mice, Inbred C57BL ; Th17 Cells/metabolism* ; Uveitis/pathology* ; Virulence

The global COVID-19 coronavirus pandemic has infected over 109 million people, leading to over 2 million deaths up to date and still lacking of effective drugs for patient treatment. Here, we screened about 1.8 million small molecules against the main protease (M^pro) and papain like protease (PL^pro), two major proteases in severe acute respiratory syndrome-coronavirus 2 genome, and identified 1851M^pro inhibitors and 205 PL^pro inhibitors with low nmol/l activity of the best hits. Among these inhibitors, eight small molecules showed dual inhibition effects on both M^pro and PL^pro, exhibiting potential as better candidates for COVID-19 treatment. The best inhibitors of each protease were tested in antiviral assay, with over 40% of M^pro inhibitors and over 20% of PL^pro inhibitors showing high potency in viral inhibition with low cytotoxicity. The X-ray crystal structure of SARS-CoV-2 M^pro in complex with its potent inhibitor 4a was determined at 1.8 Å resolution. Together with docking assays, our results provide a comprehensive resource for future research on anti-SARS-CoV-2 drug development.
Humans ; Antiviral Agents/chemistry* ; COVID-19 ; COVID-19 Drug Treatment ; High-Throughput Screening Assays ; Molecular Docking Simulation ; Protease Inhibitors/chemistry* ; SARS-CoV-2/enzymology* ; Viral Nonstructural Proteins