The occurrence of diabetes mellitus （DM） is closely related to insulin resistance and islet β cell dysfunction. Modern studies have found that macrophages are widely present in the liver，fat，skeletal muscle，islets， and other tissues and organs. Macrophage M1/M2 polarization plays an important role in the occurrence and development of diabetes mellitus and its related complications by intervening in inflammatory response，improving insulin resistance，and promoting tissue repair. Most of the traditional Chinese medicines that regulate the activation and polarization of macrophages are Qi-replenishing and Yin-nourishing，heat-clearing， and detoxicating medicinal，which are consistent with the etiology and pathogenesis of diabetes and its related complications. Therefore，by summarizing the mechanisms between macrophage activation，polarization， and insulin resistance in various tissues，this paper reviewed traditional Chinese medicine and its effective components and compounds in improving diabetes mellitus and its related complications through multi-channel regulation of macrophage polarization and regulation of M1/M2 ratio，providing references for the future treatment of DM and its related complications with traditional Chinese medicine.

Objective:To evaluate the efficacy and safety of hypomethylating agents (HMA) in patients with myelodysplastic syndromes (MDS) .Methods:A total of 409 MDS patients from 45 hospitals in Zhejiang province who received at least four consecutive cycles of HMA monotherapy as initial therapy were enrolled to evaluate the efficacy and safety of HMA. Mann-Whitney U or Chi-square tests were used to compare the differences in the clinical data. Logistic regression and Cox regression were used to analyze the factors affecting efficacy and survival. Kaplan-Meier was used for survival analysis. Results:Patients received HMA treatment for a median of 6 cycles (range, 4-25 cycles) . The complete remission (CR) rate was 33.98% and the overall response rate (ORR) was 77.02%. Multivariate analysis revealed that complex karyotype ( P=0.02, OR=0.39, 95% CI 0.18-0.84) was an independent favorable factor for CR rate. TP53 mutation ( P=0.02, OR=0.22, 95% CI 0.06-0.77) was a predictive factor for a higher ORR. The median OS for the HMA-treated patients was 25.67 (95% CI 21.14-30.19) months. HMA response ( P=0.036, HR=0.47, 95% CI 0.23-0.95) was an independent favorable prognostic factor, whereas complex karyotype ( P=0.024, HR=2.14, 95% CI 1.10-4.15) , leukemia transformation ( P<0.001, HR=2.839, 95% CI 1.64-4.92) , and TP53 mutation ( P=0.012, HR=2.19, 95% CI 1.19-4.07) were independent adverse prognostic factors. There was no significant difference in efficacy and survival between the reduced and standard doses of HMA. The CR rate and ORR of MDS patients treated with decitabine and azacitidine were not significantly different. The median OS of patients treated with decitabine was longer compared with that of patients treated with azacitidine (29.53 months vs 20.17 months, P=0.007) . The incidence of bone marrow suppression and pneumonia in the decitabine group was higher compared with that in the azacitidine group. Conclusion:Continuous and regular use of appropriate doses of hypomethylating agents may benefit MDS patients to the greatest extent if it is tolerated.

BACKGROUND/OBJECTIVES: Activating brown adipose tissue (BAT) and browning of white adipose tissue (WAT) can protect against obesity and obesity-related metabolic conditions.Cryptotanshinone (CT) regulates lipid metabolism and significantly ameliorates insulin resistance. Adenosine-5'-monophosphate (AMP)-activated protein kinase (AMPK), a receptor for cellular energy metabolism, is believed to regulate brown fat activity in humans.MATERIALS/METHODS: The in vivo study included high-fat-fed obese mice administered orally 200/400 mg/kg/d CT. They were evaluated through weight measurement, the intraperitoneal glucose tolerance test (IPGTT), intraperitoneal insulin tolerance test (IPITT), cold stimulation test, serum lipid (total cholesterol, triglycerides, and low-density lipoprotein) measurement, hematoxylin and eosin staining, and immunohistochemistry.Furthermore, the in vitro study investigated primary adipose mesenchymal stem cells (MSCs) with incubation of CT and AMPK agonists (acadesine)/inhibitor (Compound C).Cells were evaluated using Oil Red O staining, Alizarin red staining, flow cytometry, and immunofluorescence staining to identify and observe the osteogenic versus adipogenic differentiation. Quantitative real-time polymerase chain reaction and the Western blot were used to observe related gene expression. RESULTS: In the diet-induced obesity mouse model mice CT suppressed body weight, food intake, glucose levels in the IPGTT and IPTT, serum lipids, the volume of adipose tissue, and increased thermogenesis, uncoupling protein 1, and the AMPK pathway expression. In the in vitro study, CT prevented the formation of lipid droplets from MSCs while activating brown genes and the AMPK pathway. AMPK activator enhanced CT’s effects, while the AMPK inhibitor reversed the effects of CT. CONCLUSION CT promotes adipose tissue browning to increase body thermogenesis and reduce obesity by activating the AMPK pathway. This study provides an experimental foundation for the use of CT in obesity treatment.

Klebsiella pneumoniae(K.pneumoniae)is an important pathogen that can cause severe hospital-and community-acquired infections.To systematically investigate its methylation features,we determined the whole-genome sequences of 14 K.pneumoniae strains covering varying serotypes,multilocus sequence types,clonal groups,viscosity/virulence,and drug resistance.Their methy-lomes were further characterized using Pacific Biosciences single-molecule real-time and bisulfite technologies.We identified 15 methylation motifs[13 N6-methyladenine(6mA)and two 5-methylcytosine(5mC)motifs],among which eight were novel.Their corresponding DNA methyl-transferases were also validated.Additionally,we analyzed the genomic distribution of GATC and CCWGG methylation motifs shared by all strains,and identified differential distribution pat-terns of some hemi-/un-methylated GATC motifs,which tend to be located within intergenic regions(IGRs).Specifically,we characterized the in vivo methylation kinetics at single-base resolu-tion on a genome-wide scale by simulating the dynamic processes of replication-mediated passive demethylation and MTase-catalyzed re-methylation.The slow methylation of the GATC motifs in the replication origin(oriC)regions and IGRs implicates the epigenetic regulation of replication initiation and transcription.Our findings illustrate the first comprehensive dynamic methylome map of K.pneumoniae at single-base resolution,and provide a useful reference to better understand epigenetic regulation in this and other bacterial species.

OBJECTIVE：To systemat ically evaluate the efficacy and safety of Ubrogepant and Rimegepant in the treatment of acute migraine ，and to provide evidence-based reference for the clinical treatment. METHODS ：Retrieved from PubMed ，Embase， Cochrane Library ，CNKI，VIP，Wanfang database and Clinicaltrials. gov ，randomized controlled trials （RCTs） about the Ubrogepant and Rimegepant （trial group ）versus placebo （control group ）in the treatment of acute migraine were collected during the inception to Jan. 2020. After literature screening and data extraction ，quality assessment was performed using the bias risk assessment tool provided by the Cochrane system evaluator manual 5.1.0. Meta-analysis was performed by using Stata 16.0 software. RESULTS ：Eight RCTs with a total of 7 989 patients were included. The results of Meta-analysis showed that the proportion of patients who were free from pain at 2 h postdose in Ubrogepant group [RR ＝1.65，95％CI（1.38，1.98），P＜0.001] and Rimegepant group [RR ＝1.69，95％CI（1.46，1.95），P＜0.001]，the proportion of patients who were free from the most bothersome symptom at 2 h postdose in Ubrogepant group [RR ＝1.35，95％ CI（1.20，1.53），P＜0.001] and Rimegepant group [RR ＝1.37，95％CI（1.24，1.51），P＜0.001]，and other secondary outcome indicators （ i.e. the proportion of patients with pain relief at 2 h postdose ，the proportion of patients with sustained freedom from pain from 2-24 h postdose ，the proportion of patients with sustained pain relief from 2-24 h postdose ，the proportion of patients without photophobia at 2 h postdose ，the proportion of patients without phonophobia at 2 h postdose ，the proportion of patients without nausea at 2 h postdose ）were all significantly better than control group （P＜0.05）. In terms of safety ，there was no statistical significance in the incidence of total ADR between Ubrogepant group and control group [RR ＝1.04，95％CI（0.87，1.25），P＝0.646]，but the incidence of total ADR in Rimegepant group were significantly higher than control group [RR ＝1.23，95％ CI（1.01，1.50），P＝0.043]. There was no statistical significance in other security indicators （i.e. incidence of nausea ，dizziness，dry mouth ，somnolence，urinary tract infection）in 2 groups（P＞0.05）. CONCLUSIONS ：Ubrogepant and Rimegepant are effective in the treatment of acute migraine. Ubrogepant is safe ，while Rimegepant may increase the incidence of ADR.

OBJECTIVE：To systematically evaluate th e efficacy and safety of 4 kinds of calcitonin gene-related peptide （CGRP）monoclonal antibodies in the preventive treatment of migraine ，and to provide evidence-based reference for the clinical treatment of migraine. METHODS ：Retrieved from the Cochrane Library ，PubMed，Embase，CJFD，VIP and Wanfang database ， RCTs about 4 kinds of CGRP monoclonal antibodies （trial Δ 基金项目 ：四川省科技厅重点研发 （重大科技专项 ）项目 group） versus placebo （control group ） in the preventive （No.2019YFS0180） ＊硕士研究生 。研究方向 ：临床药学 、循证药学 。电话：0830- treatment of migraine were collected. After literature screening 3165787。E-mail：lewxinn@outlook.com and data extraction ， the quality evaluation of included # 通信作者：教授，硕士生导师，硕士。研究方向：临床药学、循证 literature was performed by using the bias risk assessment tool 药学。电话：0830-3165787。E-mail：hyl3160131@163.com provided by the Cochrane system evaluator manual 5.1.0. 中国药房 2020年第31卷第18期 China Pharmacy 2020Vol. 31 No. 18 ·2275· Bayesian network Meta-analysis was performed by using GeMTC 0.14.3 software and Stata 16.0 software. RESULTS ：A total of 19 RCTs involving 11 392 patients were included ，involving 10 interventions，such as Erenumab 70，140 mg/month；Fremanezumab 675 mg/3 months，225 mg/month；Galcanezumab 120，240，300 mg/month；Eptinezumab 100 mg/3 months，300 mg/3 months and placebo. Results of Meta-analysis showed that compared with control group ，4 kinds of CGRP monoclonal antibodies significantly reduced the change of mean monthly migraine days （MMD）（P＜0.05）. Among trial groups ，compared with Galcanezumab 300 mg/month [MD ＝－1.30，95％CI（－2.59，－0.05），P＜0.05] and Eptinezumab 100 mg/3 months [MD ＝－1.18， 95％CI（－2.26，－0.03），P＜0.05]，Fremanezumab 225 mg/month could significantly reduce MMD. Network Meta-analysis ranking showed that Fremanezumab 225 mg/month＞Fremanezumab 675 mg/3 months＞Galcanezumab 120 mg/month＞Erenumab 140 mg/month＞Galcanezumab 240 mg/month＞Eptinezumab 300 mg/3 months＞Erenumab 70 mg/month＞Eptinezumab 100 mg/3 months＞Galcanezumab 300 mg/month＞placebo. Compared with control group ，4 kinds of CGRP monoclonal antibodies were significantly increased of the proportion of patients whose mean monthly migraine days reduction ≥50％ compared with baseline （MMD 50）（P＜0.05）. Among trial groups ，compared with Eptinezumab 100 mg/3 months group ，MMD 50 of Fremanezumab 675 mg/3 months group [OR ＝1.51，95％CI（1.02，2.31），P＜0.05]，Fremanezumab 225 mg/month group [OR ＝1.58，95％CI （1.05，2.44），P＜0.05] were increased significantly. Network Meta-analysis ranking showed that Fremanezumab 225 mg/month＞ Fremanezumab 675 mg/3 months＞Erenumab 140 mg/month＞Galcanezumab 120 mg/month＞Eptinezumab 300 mg/3 months＞ Galcanezumab 240 mg/month＞Erenumab 70 mg/month＞Galcanezumab 300 mg/month＞Eptinezumab 100 mg/3 months＞placebo. In terms of safety ，incidence of total adverse events （AE）of trial groups receiving Fremanezumab 675 mg/3 months [OR ＝1.31， 95％CI（1.05，1.64），P＜0.05]，Galcanezumab 240 mg/month [OR ＝1.39，95％CI（1.09，1.74），P＜0.05] were significantly higher than control group. Among trial groups ，compared with Galcanezumab 240 mg/month group ，AE of Erenumab 70 mg/month group [OR ＝0.67，95％CI（0.50，0.93），P＜0.05]，Erenumab 140 mg/month group [OR ＝0.70，95％CI（0.51，0.98），P＜0.05] were decreased significantly. Compared with Fremanezumab 675 mg/3 months group ，AE of Erenumab 70 mg/month group [OR ＝ 0.72，95％CI（0.52，0.98），P＜0.05] were decreased significantly. Network Meta-analysis ranking showed that Galcanezumab 240 mg/month＞ Fremanezumab 675 mg/3 months＞Galcanezumab 120 mg/month＞Galcanezumab 300 mg/month＞Eptinezumab 300 mg/3 months＞Fremanezumab 225 mg/month＞Eptinezumab 100 mg/3 months＞placebo＞Erenumab 140 mg/month＞Erenumab 70 mg/month. CONCLUSIONS ：Four kinds of CGRP monoclonal antibodies are effective in the preventive treatment of migraine ， among which Fremanezumab 225 mg/month is most likely to have the best efficacy and Erenumab 70 mg/month is most likely to have the highest safety.

Ubiquitination, an essential post-transcriptional modification (PTM), plays a vital role in nearly every biological process, including development and growth. Despite its functions in plant reproductive development, its targets in rice panicles remain unclear. In this study, we used proteome-wide profiling of lysine ubiquitination in rice (O. sativa ssp. indica) young panicles. We created the largest ubiquitinome dataset in rice to date, identifying 1638 lysine ubiquitination sites on 916 unique proteins. We detected three conserved ubiquitination motifs, noting that acidic glutamic acid (E) and aspartic acid (D) were most frequently present around ubiquitinated lysine. Enrichment analysis of Gene Ontology (GO) annotations and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways of these ubiquitinated proteins revealed that ubiquitination plays an important role in fundamental cellular processes in rice young panicles. Interestingly, enrichment analysis of protein domains indicated that ubiquitination was enriched on a variety of receptor-like kinases and cytoplasmic tyrosine and serine-threonine kinases. Furthermore, we analyzed the crosstalk between ubiquitination, acetylation, and succinylation, and constructed a potential protein interaction network within our rice ubiquitinome. Moreover, we identified ubiquitinated proteins related to pollen and grain development, indicating that ubiquitination may play a critical role in the physiological functions in young panicles. Taken together, we reported the most comprehensive lysine ubiquitinome in rice so far, and used it to reveal the functional role of lysine ubiquitination in rice young panicles.
Acetylation ; Lysine/metabolism* ; Oryza/metabolism* ; Plant Proteins/metabolism* ; Protein Interaction Maps ; Protein Processing, Post-Translational ; Proteome/metabolism* ; Ubiquitin/metabolism* ; Ubiquitination

Objective To investigate the association of serum ghrelin level with cognition, hippocampal volume, and proton magnetic resonance spectrum ( [ 1 H ]-MRS ) in patients with type 2 diabetes mellitus ( T2DM) . Methods The T2DM patients cared at the Wuhan Fourth Hospital were recruited. Data on demographic characteristics and clinical parameters were collected. Ghrelin was measured by ELISA assay. Cognitive performance was assessed by the Montreal Cognitive Assessment ( MoCA ) and Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). The changes of metabolites in hippocampus were detected by [1 H]-MRS, including N-acetyl asparate ( NAA) , choline ( Cho) , myo-inositol ( MI) , creatine ( Cr) . All patients were divided into 2 groups[cognitive impairment (CI) and non-cognitive impairment (NCI) groups] by MoCA. Results (1) Compared with patients in NCI group, the serum ghrelin level, bilateral hippocampal volume, and NAA/Cr ratio of [1H]-MRS metabolites in CI group were decreased, but MI/Cr and Cho/Cr ratios were increased(all P<0.05). (2) Serum ghrelin was positively correlated with a variety of RBANS scores ( including immediate memory, attention, delayed memory, and total scores) , bilateral hippocampal volume, and NAA/Cr ratio of [ 1 H]-MRS metabolites in T2DM patients, but it was negatively correlated with MI/Cr ratio and Cho/Cr ratio ( all P<0. 05 ) . ( 3 ) Logistic regression analysis showed that ghrelin was a protective factor of cognition in T2DM patients. Conclusions T2DM patients with cognitive impairment had lower levels of ghrelin, and serum ghrelin was postively correlated with their cognitive performance, hippocampal volume, and [1 H]-MRS metabolites, suggesting that serum ghrelin may be involved in the occurrence and development of cognitive dysfunction in patients with T2DM.

Objective To identify the risk factors for severe acute lower respiratory infections (ALRI) in children and to provide scientific basis for prevention and treatment of ALRI. Methods Several databases including Pubmed, Databases-Medline (Ovid), Embase, CINAHL and Global Health Library, CNKI, VIP and Wanfang Date were searched (1990.1-2014.12) for references. All selected studies were about risk factors of ALRI in children. The screening and quality evalua? tion of the literature data was conducted independently by two reviewers according to the inclusion and exclusion criteria. Stata 11.0 software was used for Meta-analysis. Results Meta-analysis of 27 included literature showed that seven risk fac?tors were significantly associated with severe ALRI:low birth weight, lack of exclusive breastfeeding, crowded household, ex?posure to indoor air pollution, malnutrition, living in a house with smokers or smoking in pregnant and HIV-exposed unin?fected condition. Conclusion The above seven risk factors play the important role in the development of ALRI in children. Furthermore, it emphasizes the need for further studies investigating other potential risk factors to decrease the possibility of childhood ALRI.

Objective To investigate the prevalence of year-round respiratory viral infection in children with lower respiratory tract infection (LRTI), and the relationship between respiratory viral infection and allergen sensitization in exacerbating asthma. Methods A total of 231 hospitalized children with acute LRTI were investigated from May 2013 to April 2014. The 5 most common respiratory viruses were isolated from nasopharyngeal aspirate using multiplex reverse transcription-polymerase chain reaction, including respiratory syncytial virus (RSV), adenovirus (AV), parainfluenza virus (PIV), influenza virus (IFV) and rhinovirus (RV). Atopic sensitization was defined if more than 1 serum specific immunoglobulin E level measured using immunofluorescence experiment was over 0.35 IU/mL. Results RSV was the most common pathogen of bronchiolitis in hospitalized children through the year. RV or IFV infections were more prevalent in asthma exacerbations compared to other LRTIs. AV was more likely to cause pneumonia. RV and IFV were associated with asthma exacerbations in children with atopic sensitization, but not in nonatopic children. Conclusion RV and IFV are associated with hospitalization for asthma exacerbation in children with atopic sensitization.