Objective: To investigate the effect of targeted silencing of DNA methyltransferase 3A(DNMT3A) on collagen deposition, proliferation and migration activity of mouse lung fibroblasts(PFs). Methods: In order to ensure the proliferation and migration activity of primary fibroblasts, the lung tissues of neonatal C57 suckling mice were taken, PFs were extracted after being sheared, and the morphology was observed and identified under the microscope. PFs cells were activated by 5 ng/ml TGF-β1for 24 h after cell attachment, and DNMT3A silencing model was constructed by small interfering RNA; The experiment was divided into control group, TGF-β1group, TGF-β1+ siRNA-NC group and TGF-β1+ siRNA-DNMT3A group. The protein expressions of DNMT3A, α-smooth muscle actin(α-SMA) and Collagen Ⅰ were detected by Western blot; Real time quantitative reverse transcription polymerase chain reaction(RT-qPCR) was used to detect the mRNA expression changes ofDNMT3A,α-SMAandCollagenⅠ. The proliferation ability of PFs was detected by CCK-8 and EdU staining; the migration ability of PFs was detected by scratch test and Transwell migration test. Results: Compared with the control group, TGF-β1induced the increase of DNMT3A in the activated PFs cell group(P<0.01), the protein and mRNA levels of fibrosis and proliferation related indicators α-SMA and Collagen Ⅰ also increased(allP<0.05), and the proliferation and migration ability of PFs increased(allP<0.000 1). Compared with the siRNA-NC group, the protein expression levels of DNMT3A(P<0.000 1) and related indicators α-SMA(P<0.01) and Collagen Ⅰ(P<0.01) significantly decreased in the DNMT3A silencing group by Western blot, and the mRNA levels ofDNMT3A,α-SMAandCollagenⅠby RT-qPCR also decreased(allP<0.001), and the proliferation(P<0.01) and migration ability(P<0.05) of PFs cells decreased compared with the control group. Conclusion Silencing DNMT3A can inhibit the deposition of collagen and the proliferation of PFs. DNMT3A can promote the proliferation and migration of PFs, and then promote the activation of PFs and the development of pulmonary fibrosis. This process may be regulated by DNA methylation modification.

Animals ; Macaca mulatta ; Optic Disk ; Glaucoma ; Craniocerebral Trauma ; Intraocular Pressure ; Low Tension Glaucoma

Due to the high similarity with the lipid layer between human skin keratinocytes, functional cosmetics with layered liquid crystal structure prepared by liquid crystal emulsification technology encapsulating natural active substances have become a hot research topic in recent years. This type of functional cosmetic often has a fresh and natural skin feel, excellent skin barrier repair function and efficient moisturizing effect, etc., showing great potential in cosmetic application. However, the present research on the application of liquid crystal emulsification technology to functional cosmetics is still in the initial stage, and there are fewer relevant reports with reference values. Based on the mentioned above, this review provides a comprehensive summary of functional cosmetics with layered liquid crystal structures prepared by liquid crystal emulsification technology from the following aspects: the structure of human skin, the composition of lamellar liquid crystal, the advantages of liquid crystal emulsification technology containing natural active substances used in the field of functional cosmetics, the preparation process, main components, influencing factors during the preparation and the market functional cosmetics with lamellar liquid crystal structure. Finally, the prospect of the application of liquid crystal emulsification technology in functional cosmetics is presented, to provide useful references for those engaged in the research of liquid crystal emulsification technology-related functional cosmetics.

Objective To compare the influence between self-monitoring of blood gluocose(SMBG)combined with digital diabetes management and traditional management mode on the related clinical indexes in the patients with type 2 diabetes mellitus(T2DM).Methods A total of 100 patients with T2DM treated in the endocrinology and metabolism outpatient department of this hospital from January 2022 to June 2022 and meeting the inclusion criteria of this study were successively included.They were divided into the experimental group and control group.The experimental group was managed by SMBG combined with digital diabetes man-agement mode,while the control group adopted the traditional management mode,the outpatient clinic follow up once a month.After 6 months of follow-up,fasting blood glucose,glycosylated hemoglobin(HbA1c),low density lipoprotein cholesterol(LDL-C)and urinary microalbumin/creatinine ratio(UACR)were compared between the two groups.Results The FBG,HbA1c,LDL-C,and UACR of the experimental group decreased after intervention when compared with baseline.Compared with the control group,the FBG[8.7(7.7,9.2)mmol/L vs.10.8(8.8,12.7)mmol/L,Z=-4.660,P＜0.001],HbA1c[6.3％(5.3,7.8)％vs.8.5％(7.2,10.0)％,Z=-5.130,P＜0.001],LDL-C[2.6(1.8,3.1)mmol/L vs.3.3(2.6,4.0)mmol/L,Z=-4.112,P＜0.001],UACR[16.1(3.5,46.5)mg/g vs.58.4(11.9,108.0)mg/g,Z=-2.220,P=0.026]for patients in the expriemental group after intervention were significantly decreased.Conclusion SMBG combined with digital diabetes management model can significantly improve the clinical indicators of patients.

Objective To investigate the expression of HOXB4 gene in patients with myelodysplastic syn-dromes(MDS)and its clinical significance in disease progression.Methods mRNA expression of HOXB4 gene in bone marrow mononuclear cells was detected by real-time fluorescence quantitative PCR(RT-qPCR),and the difference in HOXB4 expression was compared between 49 patients with MDS(MDS group)and 35 patients without MDS(group C).The relationship of mRNA expression of HOXB4 with disease characteristics and clinical prognosis was explored in MDS patients.Results mRNA expression level of HOXB4 gene was higher in MDS group than that in group C(P＜0.05).The patients were divided into a high-and a low-expression group according to the median expression level of HOXB4.Leukocyte count was lower in the high-expression group in the low-expression group at the time of initial diagnosis.The proportion of patients with subtypes of primitive cellular hyperplasia,poor prognostic staging and leukemic transformation was higher in the high-expression group than in the low-expression group.Conclusions mRNA expression level of HOXB4 gene has certain relation with AML transformation in MDS patients.

ObjectiveTo explain the pharmacodynamic substances of Aurantii Fructus flavonoids that exert anti-inflammatory and analgesic effects using a structure-activity omics approach. MethodOn the basis of the previous in vitro pharmacological screening conducted by the research team， an in vivo pharmacological study of Aurantii Fructus flavonoids was carried out. Core targets of the anti-inflammatory and analgesic active components of flavonoids of Aurantii Fructus were identified using various network databases， including the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）， the Online Mendelian Inheritance in Man （OMIM）， and the Search Tool for the Retrieval of Interacting Genes/Proteins （STRING）. Computer-aided virtual screening technology was used to dock different types of Aurantii Fructus flavonoids with core targets. The key core targets with high binding activity were selected based on the comprehensive scores of each target and the active structures. Using these targets as bridges， the structures of one or more types of chemical components in Aurantii Fructus were closely linked to pharmacological effects. The structure-activity relationship between the clear pharmacodynamic compounds and their effects was explored through the binding patterns of various structures with pharmacodynamic targets. ResultAurantii Fructus flavonoids demonstrated significant anti-inflammatory and analgesic effects on dextran sulfate sodium （DSS）-induced colitis in mice， which could improve symptoms and significantly reduce the levels of inflammatory factors interleukin-6 （IL-6） and interleukin-1β （IL-1β）（P<0.05）. Twelve active components of Aurantii Fructus flavonoids were identified and categorized into nine dihydroflavonoids and three flavonoids based on their structures of the parent nuclei. Through Venn analysis， 167 anti-inflammatory and analgesic targets for Aurantii Fructus were identified. Based on degree value and molecular docking comprehensive scores， prostaglandin-endoperoxide synthase 2（PTGS2） and mitogen-activated protein kinase 3（MAPK3） were selected for further structural analysis. Structural analysis revealed that components containing glycoside structures exhibited higher binding activity with anti-inflammatory and analgesic targets. ConclusionThis study utilized a structure-activity omics approach based on in vivo pharmacodynamic experiments to analyze the material basis of the anti-inflammatory and analgesic effects of Aurantii Fructus flavonoids. The structure-activity omics approach provides new ideas and methods for elucidating the pharmacodynamic substances of Chinese medicine.

RNA editing, an essential post-transcriptional reaction occurring in double-stranded RNA (dsRNA), generates informational diversity in the transcriptome and proteome. In mammals, the main type of RNA editing is the conversion of adenosine to inosine (A-to-I), processed by adenosine deaminases acting on the RNAs (ADARs) family, and interpreted as guanosine during nucleotide base-pairing. It has been reported that millions of nucleotide sites in human transcriptome undergo A-to-I editing events, catalyzed by the primarily responsible enzyme, ADAR1. In hematological malignancies including myeloid/lymphocytic leukemia and multiple myeloma, dysregulation of ADAR1 directly impacts the A-to-I editing states occurring in coding regions, non-coding regions, and immature miRNA precursors. Subsequently, aberrant A-to-I editing states result in altered molecular events, such as protein-coding sequence changes, intron retention, alternative splicing, and miRNA biogenesis inhibition. As a vital factor of the generation and stemness maintenance in leukemia stem cells (LSCs), disordered RNA editing drives the chaos of molecular regulatory network and ultimately promotes the cell proliferation, apoptosis inhibition and drug resistance. At present, novel drugs designed to target RNA editing(e.g., rebecsinib) are under development and have achieved outstanding results in animal experiments. Compared with traditional antitumor drugs, epigenetic antitumor drugs are expected to overcome the shackle of drug resistance and recurrence in hematological malignancies, and provide new treatment options for patients. This review summarized the recent advances in the regulation mechanism of ADAR1-mediated RNA editing events in hematologic malignancies, and further discussed the medical potential and clinical application of ADAR1.

Objective:To report the results of national surveillance on the distribution and antimicrobial resistance profile of clinical Gram-negative bacteria isolates from bloodstream infections in China in 2022.Methods:The clinical isolates of Gram-negative bacteria from blood cultures in member hospitals of national bloodstream infection Bacterial Resistant Investigation Collaborative System（BRICS）were collected during January 2022 to December 2022. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute（CLSI）. WHONET 5.6 and SPSS 25.0 software were used to analyze the data.Results:During the study period，9 035 strains of Gram-negative bacteria were collected from 51 hospitals，of which 7 895（87.4%）were Enterobacteriaceae and 1 140（12.6%）were non-fermenting bacteria. The top 5 bacterial species were Escherichia coli（ n=4 510，49.9%）， Klebsiella pneumoniae（ n=2 340，25.9%）， Pseudomonas aeruginosa（ n=534，5.9%）， Acinetobacter baumannii complex（ n=405，4.5%）and Enterobacter cloacae（ n=327，3.6%）. The ESBLs-producing rates in Escherichia coli， Klebsiella pneumoniae and Proteus spp. were 47.1%（2 095/4 452），21.0%（427/2 033）and 41.1%（58/141），respectively. The prevalence of carbapenem-resistant Escherichia coli（CREC）and carbapenem-resistant Klebsiella pneumoniae（CRKP）were 1.3%（58/4 510）and 13.1%（307/2 340）；62.1%（36/58）and 9.8%（30/307）of CREC and CRKP were resistant to ceftazidime/avibactam combination，respectively. The prevalence of carbapenem-resistant Acinetobacter baumannii（CRAB）complex was 59.5%（241/405），while less than 5% of Acinetobacter baumannii complex was resistant to tigecycline and polymyxin B. The prevalence of carbapenem-resistant Pseudomonas aeruginosa（CRPA）was 18.4%（98/534）. There were differences in the composition ratio of Gram-negative bacteria in bloodstream infections and the prevalence of main Gram-negative bacteria resistance among different regions，with statistically significant differences in the prevalence of CRKP and CRPA（ χ2=20.489 and 20.252， P<0.001）. The prevalence of CREC，CRKP，CRPA，CRAB，ESBLs-producing Escherichia coli and Klebsiella pneumoniae were higher in provinicial hospitals than those in municipal hospitals（ χ2=11.953，81.183，10.404，5.915，12.415 and 6.459， P<0.01 or <0.05），while the prevalence of CRPA was higher in economically developed regions（per capita GDP ≥ 92 059 Yuan）than that in economically less-developed regions（per capita GDP <92 059 Yuan）（ χ2=6.240， P=0.012）. Conclusions:The proportion of Gram-negative bacteria in bloodstream infections shows an increasing trend，and Escherichia coli is ranked in the top，while the trend of CRKP decreases continuously with time. Decreasing trends are noted in ESBLs-producing Escherichia coli and Klebsiella pneumoniae. Low prevalence of carbapenem resistance in Escherichia coli and high prevalence in CRAB complex have been observed. The composition ratio and antibacterial spectrum of bloodstream infections in different regions of China are slightly different，and the proportion of main drug resistant bacteria in provincial hospitals is higher than those in municipal hospitals.

ObjectiveTo observe the effect of Zhengan Xifengtang on blood pressure and fecal microflora of spontaneously hypertensive rats （SHRs）. MethodA total of 75 male SHRs aged nine weeks were randomly divided into SHR group， Benazepril group （1.00 mg·kg^-1·d^-1）， high-dose Zhengan Xifengtang group （34.5 g·kg^-1·d^-1）， medium-dose Zhengan Xifengtang group （17.25 g·kg^-1·d^-1）， and low-dose Zhengan Xifengtang group （8.625 g·kg^-1·d^-1）. A total of 15 male Wistar-Kyoto （WKY） rats aged nine weeks were selected as the normal group. The normal group and SHR group were administrated with an equal volume of distilled water for eight weeks. During the administration， the blood pressure of the rats was measured regularly. After the intervention， fresh feces were collected with a sterile frozen storage tube， and 16S amplicon information was collected and analyzed. Plasma， hippocampus， and ileum of rats were collected for ultra-high performance liquid chromatography-tandem mass spectrometry（UPLC-MS/MS） detection. ResultZhengan Xifengtang decreased the systolic blood pressure and diastolic blood pressure of SHRs. Compared with the SHR group， Zhengan Xifengtang decreased the diversity of fecal microflora of SHRs. At the phylum level， Zhengan Xifengtang increased the relative abundance of SHR Verrucomicrobia and Actinobacteria and decreased the relative abundance of Synergistetes， Tenericutes， and Candidatus Saccharibacteria. Compared with the SHR group， Zhengan Xifengtang increased the relative abundance of Blautia wexlerae， Fusicatenibacter saccharivorans， and Akkermansia muciniphila and decreased the relative abundance of Clostridium lavalense， Intestinimonas butyriciproducens， Acetatifactor muris， Alloprevotella rava， and Oscillibacter valericigenes. Spearman correlation analysis showed that the systolic blood pressure of rats was negatively correlated with the relative abundance of Ethanoligenens， Aerococcus， Butyrivibrio， Olsenella， Bifidobacterium， Clostridium XIVb， Allobaculum， and Fusicatenibacter and positively correlated with the relative abundance of Alloprevotella. Zhengan Xifengtang increased the contents of plasma， hippocampal 5-hydroxy tryptamine（5-HT）， and 5-hydroxyindole acetic acid（5-HIAA） in SHRs and decreased the contents of 5-HT and 5-HIAA in the ileum， and the content of 5-HT in the hippocampus was negatively correlated with that in the ileum. ConclusionZhengan Xifengtang can reduce the blood pressure of SHRs， which may be related to reducing the diversity of SHR microflora， regulating the structure of the microflora， increasing the relative abundance of 5-HT and short-chain fatty acids bacteria， and lowering the relative abundance of pathogenic bacteria related to intestinal inflammation.

Objective To investigate the effects of electroacupuncture on the intestinal NIMA-related kinase 7(NEK7)/NOD-like receptor thermal protein domain associated protein 3(NLRP3)signaling pathway in mice with Parkinson's disease.Methods According to the randomized number table method,36 C57BL/6 mice were randomly divided into the control group,the model group,and the electroacupuncture group,with 12 mice per group.The Parkinson's disease mouse model was established by gavage of rotenone solution(10 mg/kg)for 28 d.After molding,the electroacupuncture group was stimulated with"Fengfu"(DU17),"Taichong"(LR3),and"Zusanli"(ST36)for 14 d,while the control group and the model group were only treated with immobilization.The motor ability of mice was detected by pole climbing test and hindlimb rating score,the positive expressions of nigral tyrosine hydroxylase(TH)and colon occludin were detected by immunohistochemistry,the histological morphology of colon was observed by hematoxylin-eosin staining,and Western blotting was used to detect the protein expressions of NEK7,NLRP3,Caspase-1,and interleukin-1β(IL-1β).Results Compared with the control group,mice in the model group had lower score on the pole climbing test and a higher hindlimb rating score(P＜0.01);the average optical densities of nigral TH and colon occludin were decreased(P＜0.01);significant inflammatory infiltration was observed in the colonic tissue,and the muscularis propria was thinned;and the protein expressions of NEK7,NLRP3,Caspase-1,and IL-1β in the colonic tissue were elevated(P＜0.01).Compared with the model group,mice in the electroacupuncture group had higher score on the pole climbing test and a lower hindlimb rating score(P＜0.01);the average optical densities of nigral TH and colon occludin were increased(P＜0.01);the degree of inflammatory infiltration of colonic tissues decreased,and the muscularis propria was thickened;and the protein expressions of NEK7,NLRP3,Caspase-1,and IL-1β of colonic tissues were decreased(P＜0.01).Conclusion Electroacupuncture at"Fengfu"(DU17),"Taichong"(LR3),and"Zusanli"(ST36)can improve motor functional impairments in mice with Parkinson's disease,and the mechanism may be through the inhibition of intestinal NEK7/NLRP3 pathway,improving the intestinal barrier damage,relieving the intestinal inflammation,and improving the dopaminergic neuron injury.