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Polygonati Rhizoma (PR, Huangjing in Chinese) and its processed product (PRP), which are used in Traditional Chinese medicine (TCM) for cognitive enhancement and treatment of Alzheimer's disease (AD), have not been fully explored in terms of the different mechanisms underlying their anti-AD effects. Therefore, we used APP/PS1 mice as an AD model to assess the effects of PR and PRP on anxiety-like behaviors, cognitive function, memory performance, and pathological changes in the murine brain. UPLC-HRMS was applied to identify the components of PR and PRP that entered into the blood and brain. Network pharmacology was used to elucidate potential mechanisms underlying the improvement of AD. Differences in the intestinal flora composition between mice treated with PR and PRP were investigated using 16S rRNA sequencing, establishing a correlation between pharmacological components and distinct flora profiles. The results revealed that both PR and PRP interventions ameliorated cognitive deficits and attenuated Amyloid ß (Aß) plaque deposition in the brains of AD mice. Seven specific blood-entering components, namely glutamic acid, Phe-Phe, and uridine, etc., were associated with PR intervention, whereas ten specific blood-entering components including (2R,3S)-3-isopropylmalate, 3-methylhexahydropyrrolo[1,2-a]pyrazine-1,4-dione, and 3-methoxytyrosine were related to PRP intervention. Uridine was identified as a common brain-penetrating component in both PR and PRP interventions. Network pharmacology analysis suggested that the NOD-like receptor signaling pathway, Calcium signaling pathway and Alzheimer's disease were specific pathways targeted in AD treatment using PR intervention. Moreover, the apoptosis pathway was specifically linked to AD treatment during PRP intervention. Furthermore, the administration of both PR and PRP enhanced the abundance and diversity of the intestinal flora in APP/PS1 mice. Western blotting confirmed that PR excels in regulates inflammation, whereas PRP balances autophagy and apoptosis to alleviate the progression of AD. This study offers valuable insights and establishes a robust foundation for further comprehensive exploration of the intrinsic correlation between TCM and AD.

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Purpose To explore the molecular features of diffuse large B-cell lymphoma(DLBCL)with high expression of MYC.Methods The clinical data of 45 cases of DLBCL were collected.Immunohistochemical EnVision method was used to classify the patients into the group with high expression of MYC and the group with low expression of MYC.All samples were subjected to DNA targeted sequencing and molecular typing was performed using the LymphGen online tool.Cellular origin was determined by using the Lymph2Cx method.The correlation be-tween MYC overexpression and clinicopathological parameters was analyzed by the x2 test and Fisher precise test.Survival curves were drawn and survival-related factors were analyzed u-sing Cox univariate and multivariate regression.ResultsCases were classified into DLBCL with high expression of MYC(n=17)and DLBCL with low expression of MYC(n=28).Com-pared to the group with low expression of MYC,the group with high expression of MYC had more PIM1,MYD88,CD79B,CD58 and PRDM1 mutations(76.5％vs 28.6％,70.6％vs 32.1％,58.8％vs28.6％,29.4％vs3.6％,29.4％vs 3.6％,P＜0.05),MCD were more frequently found(58.8％vs 10.7％,P=0.001),GCB were rarely found(17.6％vs 50.0％,P=0.030).Overall survival was significantly shorter in DLBCL with high expression of MYC(P＜0.05).Cox multi-factorial analysis showed that age was an independent prognostic factor for DLBCL(P＜0.05).Conclusion Patients with high expression of MYC were frequently characterized as MCD and ABC,and PIM1,MYD88,CD79B,CD58 and PRDM1 muta-tions were common.Patients with high expression of MYC had a poorer prognosis.

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Dry eye is a common chronic ocular surface disease in ophthalmology.Its pathogenesis is still not fully clar-ified,and there has been no effective prevention and treatment strategy.In recent years,with the booming development of molecular biology technologies such as gene chip technology and transcriptome sequencing technology,transcriptomic re-search on the dry eye has made some progress.In this article,we review the application of transcriptomics in dry eye re-search and explore the pathogenesis of dry eye with a view to providing new ideas for the clinical treatment of dry eye and potential targets for the development of new drugs for dry eye.

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Objective To investigate the effect of nobiletin(Nb)on lipopolysaccharide(LPS)-induced inflammatory injury of mesangium cells(HBZY-1)by regulating AMP-activated protein kinase(AMPK)/NOD-like receptor protein 3(NLRP3)signaling pathway.Methods HBZY-1 cells were separated into 5 groups:normal control(NC)group,LPS group(100 ng·mL-1 LPS),and Nb group(100 ng·mL-1 LPS+40 μmol·L-1 Nb),Rapamycin(Rap,AMPK/NLRP3 signaling pathway inhibitor)group[100 ng·mL-1 LPS+0.5 μmol·L-1 Rap],and Nb+Rap group(100 ng·mL-1 LPS+40 μmol·L-1 Nb+0.5 μmol·L-1 Rap).MTT was applied to detect the cytotoxicity and proliferation of HBZY-1 cells.ELISA was applied to detect the contents of interleukin(IL)-1β,IL-6,tumor necrosis factor-α(TNF-α),catalase(CAT),superoxide dismutase(SOD),and glutathione(GSH)in HBZY-1 cells.Flow cytometry was used to detect cell apoptosis.Western Blot was applied to detect the protein levels of AMPK/NLRP3 signaling pathway.Results Compared with the NC group,the levels of CAT,SOD,GSH,cell OD value,and the level of AMPK protein in the LPS group were significantly reduced(P＜0.05).The apoptosis rate,contents of IL-1β,IL-6,TNF-α,and the level of NLRP3 protein were significantly increased(P＜0.05).Compared with the LPS group,the levels of CAT,SOD,GSH,OD value,and the level of AMPK protein in the Nb group were significantly increased(P＜0.05).The apoptosis rate,contents of IL-1β,IL-6,TNF-α,and the level of NLRP3 protein were significantly decreased(P＜0.05),while the above indicators in the Rap group showed an opposite trend to the Nb group(P＜0.05).Compared with the Nb group,the above indicators in the Nb+Rap group also showed an opposite trend to the Nb group(P＜0.05).Conclusion Nb may alleviate LPS-induced inflammatory injury to MC cells by up-regulating the AMPK/NLRP3 signaling pathway.But down-regulation of the AMPK/NLRP3 signaling pathway may eliminate the improvement effect of Nb on LPS-induced inflammatory injury in MC cells.

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ObjectiveTo investigate the possible mechanisms of modified Xiaoyao Powder （逍遥散） in the treatment of hyperprolactinemia （HPRL） with liver constraint and spleen deficiency. MethodsNinety-six female SD rats were randomly divided into a normal group （n=16） and a modeling group （n=80）. In the modeling group， rats were subjected to chronic unpredictable stress combined with intraperitoneal injection of metoclopramide to establish a rat model of HPRL with liver constraint and spleen deficiency. The 80 successfully modeled rats were randomly divided into a model group， a high， medium， and low-dose group of modified Xiaoyao Powder， and a bromocriptine group， with 16 rats in each group. The high， medium， and low-dose groups of modified Xiaoyao Powder were orally administered doses of 60， 30， and 15 g/（kg·d） respectively， the bromocriptine group was orally administered bromocriptine tablets at a dose of 1 mg/（kg·d）， and the normal group and model group were orally administered 10 ml/（kg·d） of normal saline for 14 consecutive days. ELISA was used to detect serum prolactin （PRL） level； immunohistochemistry was used to determine the expression of tumor necrosis factor-alpha （TNF-α） and tyrosine hydroxylase （TH） in the hypothalamus； Western blot was used to detect the protein expression of tumor necrosis factor receptor 1 （TNFR1） in the hypothalamus； Real-time PCR was used to detect the mRNA expression of receptor interacting protein kinase 3 （RIP3） in the hypothalamus； immunofluorescence was used to detect the co-expression of RIP3 and dopamine neurons in the hypothalamus. ResultsCompared with the normal group， the serum PRL levels were increased in the model group， and the expression of hypothalamic TNF-α， TNFR1， RIP3 mRNA， and the co-expression of RIP3 with dopamine neurons were significantly increased， while TH expression was decreased （P＜0.05 or P＜0.01）. Compared with the model group， the expression of hypothalamic TNF-α was decreased in the bromocriptine group and low-dose group of modified Xiaoyao Powder， and the expression of TH was significantly increased in the medium and high-dose groups of modified Xiaoyao Powder and the bromocriptine group. The serum PRL levels， hypothalamic TNFR1 and RIP3 mRNA expression， and the co-expression of RIP3 with dopamine neurons were significantly decreased in all dose groups of modified Xiaoyao Powder and the bromocriptine group （P＜0.05 or P＜0.01）. Compared with the bromocriptine group， the serum PRL level were significantly increased in the high and low-dose groups of modified Xiaoyao Powder， TH expression was significantly increased in the medium-dose group of modified Xiaoyao Powder， hypothalamic RIP3 mRNA expression was decreased in the low-dose group of modified Xiaoyao Powder， and the co-expression of RIP3 with dopamine neurons was significantly increased in the high-dose group of modified Xiaoyao Powder （P＜0.01）. ConclusionModified Xiaoyao Powder can regulate the programmed cell death of hypothalamic dopamine neurons， affect DA expression， and regulate PRL levels， which may be one of its mechanisms in the treatment of HPRL with liver constraint and spleen deficiency.

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OBJECTIVE: To investigate the optimal timing of initial intravenous immunoglobulin (IVIG) treatment in Kawasaki disease (KD) patients. METHODS: KD patients were classified as the early group (day 1-4), conventional group (day 5-7), conventional group (day 8-10), and late group (after day 10). Differences among the groups were analyzed by ANOVA and Chi-square analysis. Predictors of IVIG resistance and the optimal cut-off value were determined by multiple logistic regression analyses and receiver operating characteristic (ROC) curve analysis. RESULTS: There were no significant differences in IVIG resistance among the 4 groups (p = 0.335). The sensitivity analysis also confirmed no difference in the IVIG resistance between those who started the initial IVIG ≤ day 7 of illness and those who received IVIG >day 7 of illness (p = 0.761). In addition, patients who received IVIG administration more than 7 days from the onset had a higher proportion of coronary artery abnormalities (p = 0.034) and longer length of hospitalization (p = 0.033) than those who started IVIG administration less than 7 days. The optimal cut-off value of initial IVIG administration time for predicting IVIG resistance was >7 days, with a sensitivity of 75.25% and specificity of 82.41%. CONCLUSIONS: IVIG therapy within 7 days of illness is found to be more effective for reducing the risk of coronary artery abnormalities than those who received IVIG >day 7 of illness. IVIG treatment within the 7 days of illness seems to be the optimal therapeutic window of IVIG. However, further prospective studies with long-term follow-up are required.

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Objective@#Depression was common during coronavirus disease-2019 (COVID-19) pandemic, while the association of perceived stress with depression among vaccinated healthcare workers has not been investigated. This study aimed to address this issue. @*Methods@#We included a total of 898 fully vaccinated healthcare workers during the outbreak of severe acute respiratory syndrome coronavirus 2 Delta variant in Nanjing, 2021. Depression was ascertained by Patient Health Questionnaire-9, with a cut-off score of ≥5 indicative of mild-to-severe depression. Perceived stress, resilience, and compassion fatigue were assessed by Perceived Stress Scale-10, Resilience Scale-25, and Professional Quality of Life Scale version-5, respectively. Logistic regression analyses were used to estimate the odds ratio (OR) and 95% confidence interval (CI), along with subgroup and mediation analyses. @*Results@#The prevalence of mild-to-severe depression was 41.1% in vaccinated healthcare workers. The odd of mild-to-severe depression was increased with higher perceived stress. Compared with vaccinated healthcare workers with the lowest tertile of perceived stress, those with the highest tertile had increased odds of mild-to-severe depression by 120% (OR 2.20, 95% CI 1.46 to 3.31) after multivariable-adjustment. However, perceived stress was not associated with mild-to-severe depression in vaccinated healthcare workers with strong resilience, but was in those with weak resilience (pinteraction=0.004). Further analysis showed that compassion fatigue mediated the relationship between perceived stress and mild-to-severe depression, with a mediating effect of 49.7%. @*Conclusion@#Perceived stress was related to an increased odd of mild-to-severe depression in vaccinated healthcare workers during COVID-19 pandemic, and this relationship might be explained by compassion fatigue.

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italic>Artemisia argyi (A. argyi) is a Chinese herbal medicine in China. The main active components are volatile oils, flavonoids, and other compounds, which have various pharmacological activities. Methoxylated flavonoids are the main active ingredients in A. argyi. Flavonoid O-methyltransferase (FOMT) is a key enzyme in the O-methylation of flavonoids. In order to further understand the function and characteristics of FOMT proteins, this paper carried out the whole genome mining and identification of FOMT genes in A. argyi and performed phylogenetic, chromosomal localization, gene sequence characterization, subcellular localization prediction, protein structure, gene structure analysis, and expression pattern analysis. The results showed that a total of 83 FOMT genes were identified in the genome of A. argyi. The phylogenetic tree shows that FOMT genes are divided into two subgroups, CCoAOMT (caffeoyl CoA O-methyltransferase) subfamily (32 genes) and COMT (caffeic acid O-methyltransferase) subfamily (51 genes). Gene sequence analysis showed that the number of amino acids encoded by FOMT was 70-734 aa, the molecular weight was 25 296.55-34 241.3 Da, and the isoelectric point was 4.51-9.99. Compared with 32 members of the CCoAOMT subfamily, nearly 1/3 of the 51 members of the COMT subfamily were hydrophobic proteins and 2/3 were hydrophilic proteins. Subcellular localization prediction showed that more than 80% of CCoAOMT subfamily members were located in the cytoplasm, and 96% of COMT subfamily members were located in the chloroplast. COMT subfamily members have more motifs than CCoAOMT subfamily members. The N-terminal motifs of COMT subfamily proteins are relatively variable, while the C-terminal motifs are relatively conserved. Expression pattern analysis showed that CCoAOMT subfamily members were mainly expressed in roots, while COMT members were mainly expressed in leaves. Some FOMTs showed the tissue expression specificity by real-time quantitative PCR analysis, especially in leaves. In this study, we identified and analyzed the FOMT gene family in A. argyi, and provided a theoretical basis for further research on the function of FOMTs and the biosynthesis of methylated flavonoids in A. argyi.

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Objective:To explore the relative importance of palliative care knowledge, attitude towards palliative care and healthy work environment of emergency care nurses in predicting perceived self-competence in palliative care based on dominance analysis, and to provide empirical evidence for formulating the optimal training course to improve perceived self-competence in palliative care.Methods:Totally 415 emergency care nurses from 22 tertiary hospitals in Hubei province were conducted a cross-sectional survey to complete the general information questionnaire, the Palliative Care Nursing Self-Competence Scale, the Hospice Knowledge Quiz for Nurses, the Frommelt Attitudes Toward Care of the Dying Scale Form B, and the American Association of Critical Care Nurses Healthy Work Environment Assessment Tool from January to March 2021 using convenient sampling method. Dominance analysis was used for statistical analysis.Results:The total score of perceived self-competence in palliative care of 415 emergency care nurses was (225.48 ± 60.61) points, the total score of palliative care knowledge was (12.44 ± 3.83) points, the total score of palliative care attitude was (97.35 ± 9.07) points and the total score of healthy work environment was (72.00 ± 11.99) points. Perceived self-competence in palliative care was positively associated with palliative care knowledge ( r=0.181, P < 0.01), attitude towards palliative care ( r=0.232, P<0.01) and healthy work environment ( r=0.393, P<0.01). Dominance analysis revealed that the healthy work environment, palliative care attitude and palliative care knowledge accounted for 74.15%, 14.97% and 10.88% of the variance of perceived self-competence in palliative care, respectively. Conclusions:The largest degree of prediction for emergency care nurses′ perceived self-competence in palliative care is healthy work environment, attitude next and the third is knowledge. It suggests that promoting a healthy work environment is an important way to improve nurses′ perceived self-competence in palliative care, and improving knowledge level and cultivating positive attitudes also will be better.

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Objective:To investigate the ego-depletion level of adolescents with type 1 diabetes mellitus (T1DM) and to explore its association with glycemic control and quality of life.Methods:This was a cross-sectional survey study. A total of 195 adolescents with T1DM were recruited from the First Affiliated Hospital of Nanjing Medical University from March to September 2022 by convenient sampling method. The Self-Regulatory Fatigue Scale (SRF-S) and Short Form of the Chinese version Diabetes Quality of Life for Youth Scale (C-DQOLY-SF) and the general information questionnaire were collected and the glycated hemoglobin (HbA 1c) value was detected. Results:The total score of self-regulatory fatigue for 195 adolescents with T1DM was (42.23 ± 9.94) points, with a scoring rate of 52.79%, which was at a medium level. Pearson correlation analysis showed that the total score of self-regulatory fatigue was positively correlated with HbA1c ( r = 0.25, P<0.01), and negatively correlated with quality of life ( r = -0.61, P<0.01). The hierarchical linear regression results showed that after controlling for demographic sociolagy and disease variables, ego-depletion had a positive predictive effect on HbA1c ( t = 3.69, P<0.01), while ego-depletion had a negative predictive effect on Quality of life ( t = -8.48, P<0.01). Conclusions:Ego-depletion of adolescents with T1DM may affect their blood glucose control and quality of life, which should be noticed by medical workers.

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Objective:To investigate the effect of biological maternal sounds on blood gas analysis index, mechanical ventilation time, oxygen therapy time and hospital stay in mechanically ventilated children with severe pneumonia.Methods:This study was a randomized controlled trial. From June 2020 to November 2020, 128 mechanically ventilated children with severe pneumonia in Hunan Children′s Hospital were selected by convenient sampling method and divided into four groups with 32 cases in each group by random number table method. Group A was given routine nursing care, group B was given mother sounds, group C was given mother cardiotone, group D was given biological maternal sounds. Data of blood gas analysis index, mechanical ventilation duration, oxygen therapy duration, hospital stays were collected for comparative analysis.Results:Finally, group A, B, C, and D included 28, 30, 28 and 28 cases, respectively. There was no statistically significant difference in PaO 2 among the four groups on the 1st to 2nd day after intervention ( P>0.05), but PaO 2 on the 3rd to 7th day after intervention were (75.57 ± 12.88), (77.71 ± 15.81), (78.21 ± 14.51), (78.64 ± 17.71), (79.04 ± 11.57) mmHg (1 mmHg=0.133 kPa), (81.71 ± 17.89), (82.93 ± 18.36), (82.68 ± 15.47), (83.25 ± 14.24), (83.77 ± 13.90) mmHg, (80.89 ± 18.78) (82.11 ± 13.34), (82.96 ± 14.20), (83.43 ± 14.37), (83.68 ± 12.64) mmHg, (84.54 ± 18.77), (86.29 ± 10.94), (86.96 ± 10.53), (87.46 ± 12.64), (89.08 ± 12.21) mmHg, with statistically significant differences ( F values were 41.17 - 332.68, all P<0.01). Further pairwise comparison revealed that PaO 2 in group B and group C were higher than those in group A on the 3rd to 7th day after intervention, while those in group D were higher on the 3rd to 7th day after intervention than those in group A, B, and C, with statistically significant differences( t values were 3.35- 4.75, all P<0.01). There was no statistically significant difference in PaCO 2 among the four groups on the 1st to 4th day after intervention ( P>0.05), but PaCO 2 on the 5th to 7th day after intervention was (47.31 ± 2.89), (46.18 ± 2.06), (41.94 ± 2.09) mmHg, (44.73 ± 1.76), (41.38 ± 1.30), (38.33 ± 1.16) mmHg, (44.81 ± 1.24), (41.23 ± 1.89), (38.73 ± 2.55) mmHg, (40.83 ± 1.78), (37.87 ± 1.43), (34.78 ± 2.05) mmHg, with statistically significant differences ( F=29.48, 36.12, 34.52, all P<0.05). Further pairwise comparison revealed that PaCO 2 in group B and group C were lower than those in group A on the 5th to 7th day after intervention, while PaCO 2 in group D were lower than those in groups A, B, and C, with statistically significant differences ( t values were 3.37-4.85, all P<0.01). During the analysis of PaO 2 and PaCO 2 in the four groups at different time points, the interaction effects were not statistically significant ( P>0.05). There was no significant difference in invasive mechanical ventilation duration, non-invasive mechanical ventilation duration and hospital stay among the four groups after intervention ( P>0.05). The oxygen therapy time of the four groups were (8.61 ± 6.40), (6.17 ± 4.80), (6.23 ± 2.75), and (3.75 ± 2.10) days, with statistically significant differences ( F=17.27, P<0.01). Further pairwise comparison revealed that the oxygen therapy time in group B and group C was shorter than that in group A, while group D was significantly shorter than that in groups A, B, and C, with statistically significant differences ( t values were 4.02-4.74, all P<0.01). Conclusions:Biological maternal sounds is superior to maternal sound and mother cardiotone in improve the blood gas analysis index, shorten the oxygen treatment time, which is worthy of clinical promotion in neonatal unaccompanied ward.

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Objective To observe efficacy of Zishen Ankun Granules in treatment of mice with immune premature ovarian insufficiency(POI)and its influence on cytokines interleukin 2(IL2),interleukin 6(IL6)and transforming growth factor-β(TGF-β)Methods Screening female mice with regular estrus to establish immune POI mice model with zona pellucida 3(ZP3)as antigen.Low and high doses of Zishen Ankun Granules were set up for treatment,and estradiol valerate was used as a positive control.Observing the estrous cycle of mice by papanicolaou staining,observing the morphological changes of ovarian tissues by HE staining,and detecting serum estradiol(E2),follicle-stimulating hormone(FSH),anti mullerian hormone(AMH),IL2,IL6 and TGF-β levels by ELISA.Results Compared with the blank control group,the estrous cycle of model group was prolonged and disordered,inflammatory cell were infiltrated in the ovarian stroma,growth follicles were decreased,and atresia follicles were increased(P<0.05,P<0.01);serum E2,AMH and TGF-βlevels were decreased(P<0.01),serum FSH,IL2 and IL6 levels were increased(P<0.01).Compared with model group,the estrous cycle disorder and inflammatory cell infiltration were improved in each treatment group,in which the growing follicles increased in the high dose group of Zishen Ankun and the atretic follicles decreased in the estradiol valerate group(P<0.05);serum E2,AMH and TGF-βlevels were increased in Zishen Ankun high dose group and estradiol valerate group(P<0.05,P<0.01),Serum FSH and IL6 levels in Zishen Ankun high-dose group were decreased(P<0.05),Serum IL2 levels was decreased in each treatment group(P<0.05,P<0.01).Conclusion Zishen Ankun granules can improve the levels of serum reproductive hormone,IL2,IL6 and TGF-βin immune POI mice,reduce the inflammatory response of ovary,regulate immune disorders,improve the ovarian reserve capacity,and play a protective role on the ovary.

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Objective To investigate the mutation characteristics and influencing factors of ethambutol(EMB)resistance gene of Mycobacterium tuberculosis in Guangxi Zhuang Autonomous region,and to provide evidence for molecular diagnosis and clinical treatment of tuberculosis.Methods A total of 655 strains of Myco-bacterium tuberculosis(52 ethambutol resistant strains and 603 ethambutol sensitive strains)were collected continuously from 30 TB drug resistance monitoring sites in Guangxi in 2018-2019,and the mutation characteristics and influencing factors of ethambutol resistant genes were analyzed by whole genome sequencing.Results Among 655 strains of Mycobacterium tuberculosis,54 strains had ethambutol drug resistance gene mutation,the mutation rate was 8.24%(54/655).Among 52 EMB-resistant strains detected by proportional method,21 had gene mutation,the mutation rate was 40.38%(21/52),and 33 of 603 EMB-sensitive strains had gene mutation,the mutation rate was 5.47%(33/603).The gene mutation rate in drug-resistant strains was higher than that in sensitive strains(χ2 = 77.133,P = 0.000).The coincidence rate of EMB drug resistance phenotype and gene mutation was 40.38%(21/52),and the results of the two tests were not highly consistent(Kappa = 0.343,P<0.001).The mutant genes of 54 strains were embA,embB and embC,and there were 20 mutant forms,among which 29 were mutated at unit point,accounting for 53.70%(29/54),and 25 were mutated at joint site,accounting for 46.30%(25/54).Among the unit point mutations,embB306(35.19%)had the highest mutation proportion,followed by embB497(5.56%)and embB406(3.70%).Among the joint site mutations,embC270+embB378 had the highest mutation proportion(22.22%),The second was embB306+embA-12(3.70%).Gender,anti-tuberculosis treatment history,genotype and MDR might be related to EMB gene mutation(χ2 = 9.388,P = 0.004;χ2 = 27.084,P = 0.000;χ2 = 6.671,P = 0.010;χ2 = 68.826,P = 0.000).Multivariate logistic regression analysis showed that male(OR = 6.150),retreatment(OR = 2.636)and multidrug resistance(OR = 7.333)may be risk factors for EMB resistance gene mutation,and Beijing genotype may be a protective factor for EMB resistance gene mutation(OR = 0.511).Conclusion EMB resistance of Mycobacterium tuberculosis is related to embA,embB and embC gene mutations,and the incidence of EMB resistance phenotype is not high.For male,retreatable,MDR-resistant,and non-Beijing genotype TB patients,attention should be paid to the mutation of the EMB resistance gene.

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BACKGROUND@#Islet transplantation is currently considered the most promising method for treating insulin-dependent diabetes. The two most-studied artificial islets are alginate-encapsulated b cells or b cell spheroids. As three-dimensional (3D) models, both artificial islets have better insulin secretory functions and transplantation efficiencies than cells in twodimensional (2D) monolayer culture. However, the effects of these two methods have not been compared yet. Therefore, in this study, cells from the mouse islet b cell line Min6 were constructed as scaffold-free spheroids or alginate-encapsulated dispersed cells. @*METHODS@#MIN6 cell spheroids were prepared by using Agarose-base microwell arrays. The insulin secretion level was determined by mouse insulin ELISA kit, and the gene and protein expression status of the MIN6 were performed by Quantitative polymerase chain reaction and immunoblot, respectively. @*RESULTS@#Both 3D cultures effectively promoted the proliferation and glucose-stimulated insulin release (GSIS) of MIN6 cells compared to 2D adherent cells. Furthermore, 1% alginate-encapsulated MIN6 cells demonstrated more significant effects than the spheroids. In general, three pancreatic genes were expressed at higher levels in response to the 3D culture than to the 2D culture, and pancreatic/duodenal homeobox-1 (PDX1) expression was higher in the cells encapsulated in 1% alginate than that in the spheroids. A western blot analysis showed that 1% alginate-encapsulated MIN6 cells activated the phosphoinositide 3-kinase (PI3K)/serine/threonine protein kinase (AKT)/forkhead transcription factor FKHR (FoxO1) pathway more than the spheroids, 0.5% alginate-, or 2% alginate-encapsulated cells did. The 3D MIN6 culture, therefore, showed improved effects compared to the 2D culture, and the 1% alginate-encapsulated MIN6 cells exhibited better effects than the spheroids. The upregulation of PDX1 expression through the activation of the PI3K/AKT/FoxO1 pathway may mediate the improved cell proliferation and GSIS in 1% alginate-encapsulated MIN6 cells. @*CONCLUSION@#This study may contribute to the construction of in vitro culture systems for pancreatic islets to meet clinical requirements.

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Objective:To explore the impact of PM 2.5 concentration in Shanghai on the incidence of allergic rhinitis（AR） in the population, and provide strategies for early warning and prevention of AR. Methods:Collect daily average concentrations of atmospheric pollutants monitored in Shanghai from January 1, 2017 to December 31, 2019, and clinical data of AR patients from five hospitals in Shanghai during the same period. We used a time-series analysis additive Poisson regression model to analyze the correlation between PM 2.5 levels and outpatient attendance for AR patients. Results:During the study period, a total of 56 500 AR patients were included, and the daily average concentration of PM 2.5 was（35.28±23.07）μg/m³. There is a correlation between the concentration of PM 2.5 and the number of outpatient attendance for AR cases. There is a positive correlation between the daily average number of outpatient for AR and levels of PM 2.5 air pollution（（P<0.05）） . We found that every 10 μg/m³ increase in PM 2.5, the impact of on the number of AR visits was statistically significant on the same day, the first day behind, and the second day behind, with the strongest impact being the exposure on the same day. Every 10 μg/m³ increases in PM 2.5, the number of outpatient visits increased by 0.526% on the same day（95%CI 1.000 50-1.010 04）. Conclusion:The atmospheric PM 2.5 concentration in Shanghai is positively correlated with the number of outpatient for AR, and PM 2.5 exposure is an independent factor in the onset of AR. This provides an important theoretical basis for AR.

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Background: Polycystic ovary syndrome (PCOS) is a complex class of endocrine disorders with insulin resistance, compensatory hyperinsulinemia, and obesity. However, the pathogenesis and therapies of PCOS have not been fully elucidated. Exosomal miRNAs have the potential to serve as biomarkers and therapies for a wide range of medical conditions. Method: We collected follicular fluid from 5 PCOS patients and 5 healthy people. High-throughput sequencing technology to identify differentially expressed miRNAs and untargeted metabolome identify differential metabolites in follicular fluid exosomal. RT-qPCR and AUC analysis were performed. Result: miRNA high-throughput sequencing identified 124 differential miRNAs. RT-qPCR analysis confirmed the sequencing results. These differential miRNA target genes are mainly involved in metabolic pathways. Metabolomics studies identified 31 differential metabolites. miRNA and lncRNA coexpression networks in metabolic pathways rigorously screened 28 differentially expressed miRNAs. This network would identify miRNA signatures associated with metabolic processes in PCOS. Meanwhile, the area under curve of receiver operating characteristic revealed that hsa-miR-196a-3p, hsa-miR-143-5p, hsa-miR-106a-3p, hsa-miR-34a-5p, and hsa-miR-20a-5p were potential biomarkers for the diagnosis of PCOS. Conclusion: Collectively, these results demonstrate the potential pathogenesis of PCOS, and follicular fluid exosomal miRNAs may be efficient targets for the diagnosis and treatment of PCOS in long-term clinical studies.

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Oroxin A (OA) is a flavonoid isolated from Oroxylum indicum (L.) Kurz that has various biological activities, including antioxidant activities. This study aimed to examine the viability of using OA in an in vitro culture (IVC) medium for its antioxidant effects and related molecular mechanisms on porcine blastocyst development. In this study, we investigated the effects of OA on early porcine embryo development via terminal deoxynucleotidyl transferase dUTP nick-end labeling, 5-ethynyl-2'-deoxyuridine labeling, quantitative reverse transcription PCR, and immunocytochemistry. Embryos cultured in the IVC medium supplemented with 2.5 µM of OA had an increased blastocyst formation rate, total cell number, and proliferation capacity, along with a low apoptosis rate. OA supplementation decreased reactive oxygen species levels while increasing glutathione levels. OA-treated embryos exhibited an improved intracellular mitochondrial membrane potential and reduced autophagy. Moreover, levels of pluripotency- and antioxidant-related genes were upregulated, whereas those of apoptosis- and autophagy-related genes were downregulated by OA addition. In conclusion, OA improves preimplantation embryonic development by reducing oxidative stress and enhancing mitochondrial function.

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Background/Aims@#Older adults are vulnerable to central obesity, while the association of changes in central fatness with risk of diabetes and metabolic control has not been investigated among this particular population. This study was aimed to address these issues. @*Methods@#A total of 1,815 adults aged ≥ 60 years without diabetes at baseline were followed for 4 years. Incident diabetes was ascertained based on plasma glucose, hemoglobin A1c, medical history, and/or the use of anti-diabetic drugs. Central fatness was assessed by waist circumference (WC), waist-height ratio (WHtR), and body roundness index (BRI). Logistic regression analyses were used to assess the association of changes in central fatness with risk of diabetes, along with dose-response and mediation analyses. @*Results@#During the 4-year follow-up, 177 participants developed diabetes. The risk of diabetes was increased by 42%, 41%, and 40% per 1 standard deviation increases in WC, WHtR, and BRI, respectively, in multivariable-adjusted models (all p < 0.01). Moreover, these relationships were all linearly-shaped (all pnonlinearity ≥ 0.11). Increases in WC, WHtR, and BRI correlated with increases in hemoglobin A1c, triglycerides-and-glucose index, triglycerides, white blood cell, and C-reactive protein (all p ≤ 0.04). Yet only changes in hemoglobin A1c and triglycerides-and-glucose index were identified as the possible mediators for risk of diabetes, with their mediating effect being about 35% and 21%, respectively. @*Conclusions@#Increases in central fatness were related to elevated risk of diabetes, and this association might be partly explained by the worsening of glycemic control and insulin resistance in older adults.

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Objective:To examine the association between baseline serum albumin level and short-term, long-term outcomes in patients with systemic sclerosis associated interstitial lung disease (SSc-ILD).Methods:A total of 259 patients with SSc-ILD who were hospitalized in West China Hospital of Sichuan University from January 2008 to December 2018 were enrolled. The data of serum albumin, demographic characteristics, peripheral blood hemoglobin at admission, and treatment plan were obtained from the hospital information management system, and the survival of the patients were followed up to June 1, 2019. The mean baseline serum albumin of 259 patients was 37.67 g/L, there were 118 patients with serum albumin ≤37.67 g/L (low protein group) and 141 patients with serum albumin>37.67 g/L (high protein group).Results:There were 64 males and 195 females with a mean age of 50.0(41.0, 61.0) years. The follow-up time was 627(61, 1 426) days. Compared to high protein group, the low protein group had higher proportion of male patients [30.5%(36/118) and 19.9%(28/141),χ 2=3.92, P=0.048], and higher levels of the erythrocyte sedimentation rate [45.0(27.0,69.0) vs. 29.0 (19.0,46.0)mm/1 h,χ 2=4.07, P<0.001], neutrophil percentage [71.50(63.35,77.13) vs. 65.60(59.50,72.50)%,χ 2=3.65, P<0.001], platelet [196(140,273) vs. 172(126,240)×10 9/L,χ 2=1.99, P=0.046], nutrophil/lymphocyte ratio [33.85(2.53,5.28) vs. 2.61(1.97,3.83),χ 2=4.57, P<0.001], platelet/lymphocyte ratio [149.0(112.0,216.8) vs. 113.5(72.76,158.8),χ 2=4.98, P<0.001], aspartate aminotransferase [27.0(21.0,39.0) vs. 23.0 (19.5,30.0) IU/L,χ 2=2.93, P=0.003], globulin [31.20(26.90,36.83) vs. 29.50(25.65,32.80) g/L,χ 2=2.28, P=0.023], serum cystatin C[1.14(0.98,1.33) vs. 1.02(0.88,1.16) mg/L,χ 2=3.80, P<0.001], IgA[2 710 (1 965,3 505) vs. 2 460 (1 862,3 105) mg/L,χ 2=2.13, P=0.033], IgG[15.05(12.83,21.08) vs. 13.60(11.53,17.23)g/L,χ 2=3.24, P=0.001], IgE[60.44(24.92,197.99) vs. 34.82(14.72,85.04) kIU/L,χ 2=3.33, P=0.001] and circulating immune complex [0.13(0.08,0.19) vs. 0.10(0.08,0.13)O.D,χ 2=2.60, P=0.009]; and lower levels of hemoglobin [121.5(101.8,132.0) vs. 129.0(119.0,142.0) g/L,χ 2=5.05, P<0.001], albumin [(33.28±3.49) vs.(41.34±2.95) g/L,χ 2=20.17, P<0.001] and IgM[1 320 (932,1 745) vs.1 560(1 170,2 030) mg/L, χ 2=2.63, P=0.009]. The utilization rate of antibiotics was higher in the low protein group (60 vs. 43 cases, χ 2=11.10, P=0.001). The number of patients followed up to 1, 5, and 10 years were 248, 245, and 244, respectively. The 1-year, 5-year, and 10-year cumulative survival rates of patients in low protein group and high protein group were(91.0% vs. 98.4%, χ 2=6.23, P=0.013;87.0% vs. 97.1%, χ 2=6.15, P=0.013; 81.6% vs. 97.1%, χ 2=7.00, P=0.008) respectively. Conclusions:Patients with scleroderma-associated interstitial lung disease have an increased risk of poorer prognosis when serum albumin ≤37.67 g/L.