Pharmaceutical treatment status of patients with COPD in the community based on medical Internet of Things: a real-world study.

This study aimed to investigate the real-world standardisation and adherence of medical treatment regimens in patients with chronic obstructive pulmonary disease (COPD) in the community for making future management strategy. The follow-up data and treatment information of patients with COPD, which were collected through the Management Information Center of COPD (MICCOPD) in 21 community health service centres in Songjiang District, a countryside region of Shanghai. Concordance between the pharmaceutical treatment plan and recommendation of 2017 Global Initiative for Chronic Obstructive Lung Disease (GOLD) report during the follow-up management period, as well as the medication adherence by patients,were analysed. Out of the 2044 patients diagnosed with COPD, 814 patients (39.8%) who had an initial record of medication use were found to meet the inclusion criteria. The most common medication regimens were long-acting beta-agonist plus inhaled corticosteroids (35.9%) and oral bronchodilators (41.9%). Among these 814 patients, 45.7%, 38.0%, 31.6% and 14.6% adhered to the treatment after 6, 12, 18 and 24 months of follow-up, respectively. The concordance rate with the regimens recommended by the 2017 GOLD guidelines was 35.5% at baseline, 35.5% at 6 months, 32.7% at 12 months, 35.4% at 18 months and 37% at 24 months. The compliance and guideline consistency rates of patients with COPD in the community under the management of general practitioners need to be improved. Enhancing general practitioner proficiency in the prevention and management of COPD and increasing patient awareness of the condition, are crucial standardising and improving adherence to initial and follow-up COPD treatments.

Maximizing Heterogeneous Server Utilization with Limited Availability Times for Divisible Loads Scheduling on Networked Systems.

Most of the available divisible-load scheduling models assume that all servers in networked systems are idle before workloads arrive and that they can remain available online during workload computation. In fact, this assumption is not always valid. Different servers on networked systems may have heterogenous available times. If we ignore the availability constraints when dividing and distributing workloads among servers, some servers may not be able to start processing their assigned load fractions or deliver them on time. In view of this, we propose a new multi-installment scheduling model based on server availability time constraints. To solve this problem, we design an efficient heuristic algorithm consisting of a repair strategy and a local search strategy, by which an optimal load partitioning scheme is derived. The repair strategy guarantees time constraints, while the local search strategy achieves optimality. We evaluate the performance via rigorous simulation experiments and our results show that the proposed algorithm is suitable for solving large-scale scheduling problems employing heterogeneous servers with arbitrary available times. The proposed algorithm is shown to be superior to the existing algorithm in terms of achieving a shorter makespan of workloads.

Microbiome Structure and Mucosal Morphology of Jejunum Appendix and Colon of Rats in Health and Dysbiosis.

Gut microbiota contributes to human health. Plenty of studies demonstrate that antibiotics can disrupt gut ecosystem leading to dysbiosis. Little is known about the microbial variation of appendix and its up/downstream intestine after antibiotic treatment. This study aimed to investigate the microbiome and mucosal morphology of jejunum, appendix, and colon of rats in health and dysbiosis. A rodent model of antibiotic-induced dysbiosis was employed. Microscopy was used to observe mucosal morphological changes. 16S rRNA sequencing was performed for identifying bacterial taxa and microbiome structure. The appendices of dysbiosis were found enlarged and inflated with loose contents. Microscopy revealed the impairment of intestinal epithelial cells. High-throughput sequencing showed the Operational Taxonomic Units changed from 361 ± 33, 634 ± 18, 639 ± 19 in the normal jejunum, appendix, colon to 748 ± 98, 230 ± 11, 253 ± 16 in the disordered segments, respectively. In dysbiosis, Bacteroidetes translocated inversely from the colon and appendix (0.26%, 0.23%) to the jejunum (13.87% ± 0.11%); the relative abundance of all intestinal Enterococcaceae increased, while Lactobacillaceae decreased. Several bacterial clusters were found correlated to the normal appendix, whereas nonspecific clusters correlated to the disordered appendix. In conclusion, species richness and evenness reduced in the disordered appendix and colon; similar microbiome patterns were shared between the appendix and colon regardless of dysbiosis; site-specific bacteria were missing in the disordered appendix. Appendix is likely a transit region involving in upper and lower intestinal microflora modulation. The limitation of this study is all the data were derived from rats. We must be cautious about translating the microbiome results from rats to humans.

Identification of Key Lipogenesis Stages and Proteins Involved in Walnut Kernel Development.

Walnuts are abundant in oil content, especially for polyunsaturated fatty acids, but the understanding of their formation is limited. We collected walnut (Juglans regia L.) kernels at 60, 74, 88, 102, 116, 130, and 144 days after pollination (designated S1-S7). The ultrastructure and accumulation of oil bodies (OBs) were observed using transmission electron microscopy (TEM), and the oil content, fatty acid composition, and proteomic changes in walnut kernels were determined. The oil content and OB accumulation increased during the development and rose sharply from S1 to S3 stages, which are considered the key lipogenesis stage. A total of 5442 proteins were identified and determined as differentially expressed proteins (DEPs) using label-free proteomic analysis. Fatty acid desaturases (FAD) 2, FAD3, oleosin, and caleosin were essential and upregulated from the S1 to S3 stages. Furthermore, the highly expressed oleosin gene JrOLE14.7 from walnuts was cloned and overexpressed in transgenic Brassica napus. The overexpression of JrOLE14.7 increased the oil content, diameter, hundred weight of seeds and changed the fatty acid composition and OB size of Brassica napus seeds. These findings provide insights into the molecular mechanism of oil biosynthesis and the basis for the genetic improvement of walnuts.

Physical Activity and Interpersonal Adaptation in Chinese Adolescents After COVID-19: The Mediating Roles of Self-Esteem and Psychological Resilience.

Previous studies have implied that physical activity profoundly influences interpersonal adaptation. However, this effect and its mechanisms have not been directly verified, especially for adolescents. This study examines the association between physical activity and interpersonal adaptation in adolescents through self-esteem and psychological resilience after the coronavirus disease 2019 (COVID-19) pandemic. Participants included 542 Chinese adolescents (aged 13-18 years; 242 boys and 300 girls). Adolescents in China anonymously completed a series of questionnaires, including the PARS-3 Scale of PE Activity Grade (PARS-3), the Self-esteem Scale (SES), the Resilience Scale for Adolescents (RSCA), and the Interpersonal Adaptation Scale. The results showed that physical activity positively correlated with self-esteem, psychological resilience, and interpersonal adaptation. Additionally, self-esteem and psychological resilience serially mediated the impact of physical activity on interpersonal adaptation. The findings highlight the positive impact of physical activity on adolescent interpersonal adaptation by strengthening positive psychological resources in the post-pandemic era.

Characterization of walnut JrWOX11 and its overexpression provide insights into adventitious root formation and development and abiotic stress tolerance.

The well-developed root system enables plant survival under various environmental stresses. WUSCHEL-RELATED HOMEOBOX GENE 11 (WOX11) plays a critical role in adventitious root formation and development in rice, Arabidopsis, and easy-to-root tree poplar. However, in difficult-to-root trees, the knowledge of WOX11 during adventitious root formation and development remains scarce. In this study, the JrWOX11 gene was isolated from a difficult-to-root tree walnut and heterologously expressed in the "84K" poplar. The results showed that JrWOX11 contained a similar structure and sequence to the homologous genes in rice, Arabidopsis, and poplar, but had different numbers and types of motifs and cis-elements. JrWOX11 lacked the motif GGAIQY compared to that in easy-to-root trees. In addition, JrWOX11 expression was induced by ABA, PEG, and NaCl treatments. Overexpression of JrWOX11 in poplar promoted root initiation and significantly increased adventitious root (ARs) number, lateral roots (LRs) number, and root hair (RH) length. Furthermore, the aboveground biomass was notably increased under NaCl and PEG treatments in transgenic plants. When NaCl and PEG were removed, the survival rate, aerial shoot development, and de novo root organogenesis were also markedly enhanced in transgenic shoot cuttings. The study provides valuable information on the differences between JrWOX11 and the homologous genes in rice, Arabidopsis, and poplar, and supports the critical role of JrWOX11 in the formation of AR and tolerance to salt and osmotic stresses.

Oral Microbiota Variation: A Risk Factor for Development and Poor Prognosis of Esophageal Cancer.

Recent studies have shown that oral microbiota play an important role in the esophageal cancer (EC) initiation and progression, suggesting that oral microbiota is a new risk factor for EC. The composition of the microbes inhabiting the oral cavity could be perturbed with continuous factors such as smoking, alcohol consumption, and inflammation. The microbial alteration involves the decrease of beneficial species and the increase of pathogenic species. Experimental evidences suggest a significant role of oral commensal organisms in protecting hosts against EC. By contrast, oral pathogens, especially Porphyromonas gingivalis and Fusobacterium nucleatum, give rise to the risk for developing EC through their pro-inflammatory and pro-tumorigenic activities. The presences of oral dysbiosis, microbial biofilm, and periodontitis in EC patients are found to be associated with invasive cancer phenotypes and poor prognosis. The mechanism of oral bacteria in EC progression is complex, which involves a combination of cytokines, chemokines, oncogenic signaling pathways, cell surface receptors, the degradation of extracellular matrix, and cell apoptosis. From a clinical perspective, good oral hygiene, professional oral care, and rational use of antibiotics bring positive impacts on oral microbial balance, thus helping individuals reduce the risk of EC, inhibiting postoperative complications among EC patients, and improving the efficiency of chemoradiotherapy. However, current oral hygiene practices mainly focus on the oral bacteria-based predictive and preventive purposes. It is still far from implementing microbiota-dependent regulation as a therapy for EC. Further explorations are needed to render oral microbiota a potential target for treating EC.

A genome variation map provides insights into the genetics of walnut adaptation and agronomic traits.

BACKGROUND: Common walnut (Juglans regia L.) is one of the top four most consumed nuts in the world due to its health benefits and pleasant taste. Despite its economic importance, the evolutionary history and genetic control of its adaptation and agronomic traits remain largely unexplored. RESULTS: We report a comprehensive walnut genomic variation map based on whole-genome resequencing of 815 walnut accessions. Evolutionary analyses suggest that Chinese J. regia diverged from J. sigillata with extensive hybridizations after the split of the two species. In contrast to annual crops, the genetic diversity and heterozygous deleterious mutations of Chinese common walnut trees have continued to increase during the improvement process. Selective sweep analyses identify 902 genes uniquely selected in the improved common walnut compared to its progenitor population. Five major-effect loci are identified to be involved in walnut adaptations to temperature, precipitation, and altitude. Genome-wide association studies reveal 27 genomic loci responsible for 18 important agronomic traits, among which JrFAD2 and JrANR are the potentially major-effect causative genes controlling linoleic acid content and color of the endopleura of the nut, respectively. CONCLUSIONS: The largest genomic resource for walnuts to date has been generated and explored in this study, unveiling their evolutionary history and cracking the genetic code for agronomic traits and environmental adaptation of this economically crucial crop tree.

Rejuvenation remodels transcriptional network to improve rhizogenesis in mature Juglans tree.

Adventitious rooting of walnut species (Juglans L.) is known to be rather difficult, especially for mature trees. The adventitious root formation (ARF) capacities of mature trees can be significantly improved by rejuvenation. However, the underlying gene regulatory networks (GRNs) of rejuvenation remain largely unknown. To characterize such regulatory networks, we carried out the transcriptomic study using RNA samples of the cambia and peripheral tissues on the bottom of rejuvenated and mature walnut (Juglans hindsii × J. regia) cuttings during the ARF. The RNA sequencing data suggested that zeatin biosynthesis, energy metabolism and substance metabolism were activated by rejuvenation, whereas photosynthesis, fatty acid biosynthesis and the synthesis pathways for secondary metabolites were inhibited. The inter- and intra-module GRNs were constructed using differentially expressed genes. We identified 35 hub genes involved in five modules associated with ARF. Among these hub genes, particularly, beta-glucosidase-like (BGLs) family members involved in auxin metabolism were overexpressed at the early stage of the ARF. Furthermore, BGL12 from the cuttings of Juglans was overexpressed in Populus alba × P. glandulosa. Accelerated ARF and increased number of ARs were observed in the transgenic poplars. These results provide a high-resolution atlas of gene activity during ARF and help to uncover the regulatory modules associated with the ARF promoted by rejuvenation.

Comparison of microbiomes in ulcerative and normal mucosa of recurrent aphthous stomatitis (RAS)-affected patients.

BACKGROUND: Recurrent aphthous stomatitis (RAS) is the most common form of oral ulcerative disease, whose cause is still unknown. Researchers have found the association of many factors with the occurrence of RAS, and proposed oral bacterial infection could be a cause for this disease. METHODS: To investigate whether the occurrence of RAS is associated with oral bacterial infection, we performed high throughput sequencing analysis of bacterial samples collected from the normal oral mucosa and aphthous ulcers of 24 patients. RESULTS: Firmicutes, Proteobacteria and Bacteriodetes were the most abundant phyla in the microbiomes analysed. The alpha diversities of the oral mucosa and aphthous ulcer microbiomes were similar, suggesting a similar richness and diversity. The NMDS analysis showed the oral mucosa and aphthous ulcer microbiomes are significantly different. This suggestion is further supported by Anosim, MRPP, and Adonis analyses. More detailed comparison of the two groups of microbiomes suggested that the occurrence of RAS is significantly associated with the increase of Escherichia coli and Alloprevotella, as well as the decrease of Streptococcus. CONCLUSIONS: Considering E. coli is a very common intestinal bacterium, we propose that E. coli colonization could be a cause for RAS, and controlling E. coli colonization could help curing RAS.

Soil Chemical and Microbiological Properties Are Changed by Long-Term Chemical Fertilizers That Limit Ecosystem Functioning.

Although the effects of fertilization and microbiota on plant growth have been widely studied, our understanding of the chemical fertilizers to alter soil chemical and microbiological properties in woody plants is still limited. The aim of the present study is to investigate the impact of long-term application of chemical fertilizers on chemical and microbiological properties of root-associated soils of walnut trees. The results show that soil organic matter (OM), pHkcl, total nitrogen (TN), nitrate-nitrogen (NO3-), and total phosphorus (TP) contents were significantly higher in non-fertilized soil than after chemical fertilization. The long-term fertilization led to excessive ammonium-nitrogen (NH4+) and available phosphorus (AP) residues in the cultivated soil, among which NH4+ resulted in soil acidification and changes in bacterial community structure, while AP reduced fungal diversity. The naturally grown walnut trees led to an enrichment in beneficial bacteria such as Burkholderia, Nitrospira, Pseudomonas, and Candidatus_Solibacter, as well as fungi, including Trichoderma, Lophiostoma, Phomopsis, Ilyonectria, Purpureocillium, Cylindrocladiella, Hyalorbilia, Chaetomium, and Trichoglossum. The presence of these bacterial and fungal genera that have been associated with nutrient mobilization and plant growth was likely related to the higher soil OM, TN, NO3-, and TP contents in the non-fertilized plots. These findings highlight that reduced chemical fertilizers and organic cultivation with beneficial microbiota could be used to improve economic efficiency and benefit the environment in sustainable agriculture.

The complete chloroplast genome of paradox (Juglans major × J. regia), an interspecific hybrid in China.

Paradox is one of the most important rootstock resources in USA and China walnut industry. In this study, we characterized the complete chloroplast genome of Paradox (Juglans major × J. regia) based on next generation sequencing. The circular complete chloroplast genome was 160,324 bp in length, containing a large single-copy (LSC) region of 89,852 bp, and a small single-copy (SSC) region of 18,410 bp. These two regions were separated by a pair of inverted repeat regions (IRa and IRb) of 26,031 bp each. A total of 131 functional genes were encoded, consisted of 87 protein-coding genes, 36 tRNA genes, and 8 rRNA genes. The overall GC content of the chloroplast genome was 36.1% and the GC contents of the LSC, SSC, and IR regions were 33.7, 29.9, and 42.6%, respectively. The phylogenetic analysis by Neighbor-Joining showed that Paradox was relatively closely related to J. major compared to other species of Juglans genus. This complete chloroplast genome will provide valuable insight into evolution, molecular breeding, and phylogenetic analysis of Juglans species.

The effect of smear layer removal on E. faecalis leakage and bond strength of four resin-based root canal sealers.

BACKGROUND: The aim of the study was to assess bacterial sealability and bonding ability of methacrylate-based Resilon (RS, SybronEndo), Endo Rez (ER, Ultradent Products Inc), and epoxy-based AH Plus (AH, Dentsply/DeTrey), MTA Fill Apex (MTAF, Angelus Soluções Odontológicas) root canal sealers, and the effect of the smear layer removal on the sealability. METHODS: One hundred thirty root segments were instrumented up to apical size #60 and rinsed with 2.5% NaOCl. Half of the roots were rinsed with 5ml 17% EDTA to remove the smear layer. All the roots were filled with AH, ER, MTAF sealers and gutta-percha, or RS with Resilon cones. After storage at 37°C for 7 days the samples were mounted into bacterial leakage assay for 50 days. Another 100 roots were instrumented and rinsed as described above, split longitudinally, cut into the cervical, middle and apical parts. The sealers were injected through the plastic mould on the dentin surface. After 7 days of incubation at 37°C, bond strength was tested using a notched-edge test fixture (Crosshead, Ultradent Products Inc.) and a universal testing machine (Lloyd Instruments). RESULTS: AH revealed the longest mean time for bacterial resistance by 29.4 and 36.8 days (with and without smear layer, respectively) followed by RS (15.1 and 24.7 days, respectively). The difference between materials was significant (p<0.001). Bond strength values ranged from 0.2± 0.1 to 3.5± 0.7 MPa and increased from the apical to the cervical third. In the apical third, AH showed the highest mean (SD) bond values 1.4 (0.4) MPa and 1.7 (0.6) MPa (with and without smear, respectively, followed by RS, 0.5 (0.1) MPa and 0.8 (0.1) MPa, respectively. The difference between materials was significant (p=0.001). CONCLUSION: The effect of the smear layer removal on the sealability was material-dependent.

Reduced peak stimulated growth hormone is associated with hyperuricemia in obese children and adolescents.

The purpose of the study is to investigate whether reduced peak GH response to arginine-levodopa test is associated with hyperuricemia in obese children and adolescents. The study population consisted of a total sample of 78 obese and 30 normal-weight children and adolescents without known hypopituitarism. All participants underwent clinical examination and GH stimulation testing. IGF-1, lipid profile and other metabolic markers were assessed. The obese subjects were then divided into two groups according to the serum levels of uric acid. Results show that obese subjects had significantly lower peak GH, lower IGF-1 and similar height SDS than those in the control group. Children with hyperuricemia had significantly lower peak stimulated GH compared with non-hyperuricemia obese subjects. Results from logistic regression model showed that peak GH were negatively associated with hyperuricemia after controlling for age, gender, tanner stage, BMI SDS, IGF-1, blood pressure, HOMA-IR, lipids status. These data indicate that lower peak GH is positively associated with hyperuricemia in obese children and adolescents without known hypothalamic/pituitary disease after controlling BMI and insulin resistance, as well as other cardiometabolic risk factors.

Gut Microbiome Associates With Lipid-Lowering Effect of Rosuvastatin in Vivo.

Background: Statin has been widely used to treat hyperlipidemia because of its high potency in decreasing cholesterol levels. The present study aimed to examine the lipid-lowering effect of rosuvastatin and the composition, diversity and species abundance of gut microbiome in association with rosuvastatin efficacy. TRIAL REGISTRATION: ChiCTR-ORC-17013212 at the First Affiliated Hospital of Dalian Medical University, November 2, 2017. Results: Totally 64 patients with hyperlipidemia were treated with 10 mg/day of rosuvastatin for 4-8 weeks. Blood lipid indicators triglycerides (TG), total cholesterol (TC), high density lipoprotein (HDL), low-density lipoprotein cholesterol (LDL-C) were measured before and after the treatment. Stool samples were collected right after the treatment. Following total DNA extraction and PCR amplification of 16S rRNA gene, Illumina sequencing was performed for gut microbiome identification, classification and characterization. All the patients showed a significant blood lipid reduction after the treatment. The patients were grouped according to parallel manner design. Group I had 33 patients whose blood lipid levels dropped to the normal levels from week 4, with 58.5% reduction in LDL-C and 26.6% reduction in TC. Group II had 31 patients whose blood lipid levels were still above the normal levels after 8 weeks therapy, but with 41.9% reduction in LDL-C and 31.2% reduction in TC. Based on Operational Taxonomic Unit data, Alpha-diversity by Shannon Index was different between the two groups, and beta-diversity by Principle Component Analysis exhibited separated patterns of the two groups. The differences were also observed in the relative-abundance at phylum, family, and genus levels of the two groups. Linear discriminate analysis illustrated that the abundance of 29 taxa was higher in group I, while the abundance of other 13 taxa was higher in group II. Phyla Firmicutes and Fusobacteria had negative correlation to LDL-C level, but Cyanobacteria and Lentisphaerae had a positive correlation to LDL-C level. Moreover, gender and age were also found somehow correlated to microbial community composition. Conclusion: Rosuvastatin therapy had different blood lipid-lowering effect on hyperlipidemia. The gut microbiota exhibited variation in community composition, diversity and taxa in association to rosuvastatin hypolipidemic effect. These results indicate that modulation of gut microflora, especially the negative/positive correlated species might strengthen statin efficacy in statin-inadequate patients.

A novel rejuvenation approach to induce endohormones and improve rhizogenesis in mature Juglans tree.

BACKGROUND: Juglans is a difficult-to-root tree. In the present study, we successfully rejuvenated stock plants by grafting and then burying them horizontally. RESULTS: Rooting rates of rejuvenated shoots were 98.1% 20 days after cutting. We recorded spatial and temporal variation in endogenous indole-3-acetic acid (IAA), abscisic acid (ABA), gibberellin A3 (GA3) and zeatin-riboside (ZR) under root induction. The four types of endohormones were mainly confined to the phloem sieve and companion cells (S&Cs) at the base of either rejuvenated or mature soft shoots. IAA and ABA levels were higher in rejuvenated shoots than in mature shoots, whereas the opposite was true for GA3 and ZR. During rooting induction, GA3 was the first hormone to be observed outside phloem S&Cs, followed by IAA, ABA and ZR. In rejuvenating soft shoots, IAA accumulated in the cross-sectional areas of the cambium and phloem, where root primordia were evident. CONCLUSIONS: The improvement in the rooting ability that was evident after rejuvenation most likely results a transformation of the plant to a juvenile form, from elevated IAA levels in phloem S&Cs and from a promotion of all four endohormones outside phloem S&Cs, in particular, from an accumulation of IAA in the cross-sectional areas of the cambium and phloem.

Reduced Growth Hormone Secretion is Associated with Nonalcoholic Fatty Liver Disease in Obese Children.

The purpose of the study was to evaluate the relationship between arginine-levodopa-induced growth hormone (GH) secretion and nonalcoholic fatty liver disease (NAFLD) in obese children. This study includes a total of 84 obese and 43 normal weight children. The obese subjects are divided into two groups based on the presence or absence of NAFLD. Clinical examination, anthropometric and laboratory examinations, and liver ultrasonography are assessed for all participants. The obese group had significantly lower peak stimulated GH (p<0.001) and lower insulin-like growth factor 1 (IGF-1) (p<0.001) compared with the control group. Children with NAFLD had significantly lower peak stimulated GH (p<0.001) and lower IGF-1 (p=0.022) compared with non-NAFLD group. Results from logistic regression model showed that only peak GH after stimulation test was inversely associated with NAFLD (p=0.015), while body mass index (BMI) was positively associated with NAFLD (p=0.03). Among 84 obese children and adolescents, peak stimulated GH was negatively associated with alanine aminotransferase (r=-0.394, p<0.001), BMI (r=-0.571, p<0.001), systolic blood pressure (r=-0.223, p=0.041), diastolic blood pressure (r=-0.272, p=0.012), homeostasis model assessment of insulin resistance (r=-0.369, p=0.001), insulin (r=-0.382, p<0.001), and positively associated with high density lipoprotein cholesterol (r=0.275, p=0.011). Our study confirms a significant inverse relationship between NAFLD and GH response to standard stimulation testing in obese children without known hypothalamic/pituitary disease.

The Genetic Structures of an Extensively Drug Resistant (XDR) Klebsiella pneumoniae and Its Plasmids.

Multi-, extensively-, and pan-drug resistant bacteria are a threat to our health today, because their wide resistance spectra make their infections difficult to cure. In this work, we isolated an extensively drug resistant (XDR) Klebsiella pneumoniae 2-1 strain from the stool sample of a patient diagnosed of colorectal cancer. K. pneumoniae 2-1 was found to be resistant to all the antibiotics tested except for cefepime, tigecycline, and ceftazidime-avibactam. By sequencing the complete genome of K. pneumoniae 2-1, we found it contains a chromosome of 5.23 Mb and two circular plasmids with the size of 246 and 90 kb. The larger plasmid, pKP21HI1 was found to be a new conjugation-defective plasmid belonging to incompatibility group HI1B and a new sequence type. Further comparative genomics analysis and antimicrobial resistance gene analysis showed that although a great deal of changes took place on the chromosome of K. pneumoniae 2-1 in comparison with the reference genome, the extensively drug resistance phenotype of K. pneumoniae 2-1 is primarily due to the two multidrug resistant plasmids it contains. This work explains the genetic and mechanistic basis of the extensive drug resistance of K. pneumoniae 2-1, and found that plasmids play key roles in the strong antibiotic resistance of bacteria.