Discovery of BIO-8169─A Highly Potent, Selective, and Brain-Penetrant IRAK4 Inhibitor for the Treatment of Neuroinflammation.

Interleukin receptor associated kinase 4 (IRAK4) plays an important role in innate immune signaling through Toll-like and interleukin-1 receptors and represents an attractive target for the treatment of inflammatory diseases and cancer. We previously reported the development of a potent, selective, and brain-penetrant imidazopyrimidine series of IRAK4 inhibitors. However, lead molecule BIO-7488 (1) suffered from low solubility which led to variable PK, compound accumulation, and poor in vivo tolerability. Herein, we describe the discovery of a series of pyridone analogs with improved solubility which are highly potent, selective and demonstrate desirable PK profiles including good oral bioavailability and excellent brain penetration. BIO-8169 (2) reduced the in vivo production of pro-inflammatory cytokines, was well tolerated in safety studies in rodents and dog at margins well above the predicted efficacious exposure and showed promising results in a mouse model for multiple sclerosis.

Prognostic significance of systemic immune inflammatory index in NSCLC: a meta-analysis.

Aim: The aim of this meta-analysis was to investigate the relationship between the baseline systemic immune inflammatory index (SII) and prognosis in patients with NSCLC. Materials & methods: The relation between pretreatment SII and overall survival, disease-free survival, cancer-specific survival, progression-free survival and recurrence-free survival in NSCLC patients was analyzed combined with hazard ratio and 95% CI. Results: The results showed that high SII was significantly correlated with overall survival and progression-free survival of NSCLC patients, but not with disease-free survival, cancer-specific survival and recurrence-free survival. Conclusion: The study suggests that a higher SII has association with worse prognosis in NSCLC patients. PROSPERO registration number: CRD42022336270.

Qualities of Older Adults' Family and Friendship Relationships and Their Association with Life Satisfaction.

While family and friendship relationship qualities are associated with life satisfaction, evidence on how these types of relationships interact to contribute to older adults' life satisfaction is sparse. This study examined how family and friendship relationship qualities may be supportive of (compensatory) or conflict with (competing) older adults' life satisfaction. We adopted a cross-sectional design to analyze data from the Health and Retirement Study (n = 1178, females = 54.8%, mean age = 67.9 years, SD = 9.3 years) to examine compensatory (as in social support) and competing (as in social strain) qualities of family and friendship social relationships and their association with life satisfaction in older adults. For greater explanatory power, we also controlled for life satisfaction by sociodemographic variables of age, gender, education, self-reported general health, physical health and activity, depression, and personality traits. Our findings indicate that the spouse/partner support relationship contributes to older adults' life satisfaction overall and is associated with greater social support and less social strain. Friendship support is associated with improved life satisfaction for older adults reporting spouse/partner strain. Relationship support for the life satisfaction of older adults should consider their need for social support from their social network while minimizing the risk of social strain from adversarial relationships in life situations.

The novel HLA-A*24:627 allele, identified by Sanger dideoxy nucleotide sequencing in a Chinese individual.

The HLA-A*24:627 allele differs from HLA-A*24:02:01:01 by one nucleotide substitution in codon 172 in exon 2.

Nematicidal Activity of 20-Deoxyingenol-3-angelate from Euphorbia peplus Latex Through Protein Kinase C Isotype TPA-1.

The latex of Euphorbia peplus and its major component 20-deoxyingenol-3-angelate (DI3A) displayed significant nematicidal activity against Caenorhabditis elegans and Panagrellus redivivus. DI3A treatment inhibited the growth and development of nematodes and caused significantly negative effects on locomotion behavior, reproduction, and accumulation of reactive oxygen species. Transcriptome analysis indicated that differential expression genes in DI3A-treated C. elegans were mainly associated with the metabolism, growth, and development process, which were further confirmed by RT-qPCR experiments. The expression level of TPA-1 gene encoding a protein kinase C isotype was obviously upregulated by DI3A treatment, and knockdown of TPA-1 by RNAi technology in the nematode could relieve the growth-inhibitory effect of DI3A. Metabolic analysis indicated that DI3A was hardly metabolized by C. elegans, but a glycosylated indole derivative was specifically accumulated likely due to the activation of detoxification. Overall, our findings suggested that DI3A from E. peplus latex exerted a potent nematicidal effect through the gene TPA-1, which provides a potential target for the control of nematodes and also suggests the potential application value of E. peplus latex and DI3A as botanical nematicides.

Digital health literacy and associated factors among internet users from China: a cross-sectional study.

BACKGROUND: As the internet develops and 5G technology becomes increasingly prominent, the internet has become a major source of health-related information. Increasingly, people use the internet to find health-related information, and digital health literacy is now a set of essential capabilities to improve their health in the digital era. However, little is known about the factors that influencing digital health literacy. This study aimed to assess digital health literacy scores and identify its influencing factors among internet users in China. Additionally, this study explored the participant's actual skills using an additional set of performance-based items from the Digital Health Literacy Instrument (DHLI). METHODS: An online cross-sectional study was conducted in August 2022. Participants aged ≥18 years were recruited to complete the survey. Data were collected using the Chinese revised version of the DHLI, the self-reported internet use questionnaire, and the sociodemographic questionnaire. We conducted multivariate linear regression analyses to explore the relationships among the sociodemographic variables, behavior of internet use, and the digital health literacy scores. RESULTS: In total, 702 participants completed the survey. The mean DHLI score was 2.69 ± 0.61. Multivariate linear regression analyses showed that the age groups 35-49 (ß = - 0.08, P = 0.033), 50-64 (ß = - 0.161, P < 0.001), and ≥ 65 (ß = - 0.138, P < 0.001) were negatively associated with DHL scores. However, education level, including bachelor's or associate degree (ß = 0.255, P = 0.002) and master's degree and above (ß = 0.256, P < 0.001), frequency of health-related Internet usage (ß = 0.192, P < 0.001), the number of digital devices used (ß = 0.129, P = 0.001), and OHISB (ß = 0.103, P = 0.006) showed a positive relationship with DHL scores. CONCLUSIONS: The study findings demonstrate that age, educational levels, number of technological devices used, and greater use of the web for health information were independently associated with DHL scores. Healthcare providers should consider providing training programs tailored to specific sociodemographic factors to improve the ability that find and use accurate information online to meet digital health services, which contributes to enhance their self-management and reduce health disparities.

Investigating the correlation of delirium after cardiac surgery with memories and posttraumatic stress disorder consequences of intensive care unit: A prospective cohort study.

OBJECTIVES: To explore the differences in post-intensive care unit memory and posttraumatic stress disorder symptoms between patients with and without delirium, and assess the correlations between the two. DESIGN: Prospective cohort observation study. SETTING: A cardiac intensive care unit of a tertiary hospital in China. We enrolled 318 consecutive patients after cardiac surgery between December 2017 and March 2019. MAIN OUTCOME MEASURES: Delirium was assessed using the Confusion Assessment Method for the ICU from intensive care unit admission to discharge. Intensive care unit memory was assessed using the ICU-Memory Tool through face-to-face interviews one week after discharge. Posttraumatic stress disorder was measured telephonically using the Impact of Events Scale-revised questionnaire at three months post-discharge. RESULTS: Eighty patients each in the delirium and non-delirium groups were enrolled for follow-up interviews. Patients with delirium had vaguer memories of pre-intensive care unit admission and of their stay, and recollected more memories of feelings (vs. without delirium). Posttraumatic stress disorder was diagnosed in 14 patients with and in seven without delirium, with non-significant differences between groups. Delirium did not influence post-intensive care unit factual, feeling, and delusional memories, nor posttraumatic stress disorder and hyperarousal, intrusion, and avoidance. The memories of feelings were positively correlated with the last three (r = 0.285, r = 0.390 and r = 0.373, respectively). CONCLUSION: Patients with delirium had vague intensive care unit memories. Memories of feelings were positively correlated with symptoms of hyperarousal, intrusion, and avoidance. Delirium did not influence factual, feeling, or delusional memories nor posttraumatic stress disorder incidence and symptoms. IMPLICATIONS FOR CLINICAL PRACTICE: Interventions are needed to reduce the impact of vague memory in patients with post-intensive care unit delirium. Memories of feelings should be focused on because of their correlation with hyperarousal, intrusion, and avoidance. Delirium prevention and early recognition measures are suggested.

Effect of cardiac function in patients with gastrointestinal cancer with or without acute kidney injury assessed using a non-invasive impedance cardiography: a case-control study.

OBJECTIVES: This study aimed to analyze the possible causes of changes in cardiac function and investigate the feasibility of clinical assessment of gastrointestinal cancer in patients with or without acute kidney injury (AKI) assessed using a non-invasive impedance cardiography (ICG, Bioz. Cardio Dynamics, USA) to identify independent risk factors. METHODS: Patients admitted to the Fourth Hospital of Hebei Medical University, China, between May 1, 2019, and February 15, 2022, were included in this study. A total of 51 patients with gastrointestinal cancer (31 men and 20 women, mean age 61.1 ± 10.9 years) with or without AKI were evaluated for ICG. A total of 19 patients underwent ultrasound cardiography (UCG) and ICG evaluations. RESULT: There was a significant positive correlation between cardiac output (CO), cardiac index (CI), stroke volume (SV), left cardiac work index (LCWI), and ejection fraction (EF) measured using UCG and ICG. The relationship was observed between COICG and COUCG (r = 0.707, P = 0.001), CIICG and CIUCG (r = 0.718, P = 0.001), SVICG and SVUCG (r = 0.837, P < 0.001), and LCWIICG and EFUCG (r = 0.540, P = 0.017). Cardiac function parameters measured using ICG were statistically different between patients with gastrointestinal cancer with or without AKI (P ≤ 0.05). Multivariate analysis revealed that AKI independently affects cardiac function in patients with gastrointestinal cancer. CONCLUSIONS: UCG and ICG methods are significantly associated with cardiac function in patients with or without AKI, and patients with gastrointestinal cancer with AKI are worse than those without AKI. AKI is an independent risk factor for cardiac function in patients with gastrointestinal cancer.

Clinicopathological study of malignant peripheral nerve sheath tumors in the head and neck: Case reports and review of literature.

BACKGROUND: Malignant peripheral nerve sheath tumor (MPNST) is a rare and aggressive soft tissue sarcoma that poses a major diagnostic and therapeutic challenge. CASE SUMMARY: We retrospectively reviewed patients with head and neck MPNSTs treated in our hospital from 2000 to 2021. The clinical features, pathological manifestations, treatments, and prognoses were summarized. We also reviewed the literature, focusing on MPNST in the mandible and maxilla. The study population consisted of five women and five men aged 22-75 years (mean age, 49 years). Of the 10 patients, 7 were initial cases and 3 were recurrent cases. All lesions were sporadic. The most common site was the mandible. The most frequently encountered symptoms were a progressive mass and local swelling. Complete or partial loss of trimethylation at lysine 27 of histone H3 (H3K27me3) was evident on staining in four of nine cases (one case was excluded due to lack of tissue for evaluation of loss of H3K27me3). The 2- and 5-year disease-specific survival rates were 86% and 43%, respectively. The average survival time was 64 mo. CONCLUSION: MPNST is a highly malignant tumor with a poor prognosis, prone to a high risk of recurrence and distant metastasis. Complete surgical resection is the main treatment.

Sarcopenia is associated with non-motor symptoms in Han Chinese patients with Parkinson's Disease: a cross-sectional study.

BACKGROUND: Sarcopenia is commonly seen in the older adults and increases in incidence with age, also in Parkinson's disease (PD). Although research has indicated that the development of sarcopenia in patients with PD may be related to both motor symptoms and non-motor symptoms (NMS), the precise relationship between the two conditions remains unclear. Therefore, we aimed to investigate the incidence of sarcopenia in patients with PD and its association with NMS. METHODS: The study included 123 patients with PD and 38 age- and sex-matched healthy controls (HC). All participants were evaluated for sarcopenia using the 2019 Asian Sarcopenia Diagnostic Criteria, and patients with PD underwent standard assessments of motor symptoms and NMS. Multiple logistic regression and receiver operating characteristic (ROC) curve analyses were used to examine the association between sarcopenia and NMS in patients with PD. RESULTS: The incidence of sarcopenia was significantly higher in patients with PD than in HC (26.8% vs. 10.4%, p = 0.046). Multiple logistic regression analysis revealed that poorer sleep quality (odds ratio [OR]: 1.245; 95% confidence interval [CI]: 1.011-1.533; p = 0.040) and fatigue (OR: 1.085, 95% CI: 1.006-1.170, p = 0.034) were independently associated with sarcopenia. ROC analysis indicated that the optimal cut-off value for Pittsburgh Sleep Quality Index (PSQI) scores was 10, with 72.7% sensitivity and 74.4% specificity (area under the curve [AUC] = 0.776, 95% CI: 0.683-0.868, p < 0.001). The optimal cut-off value for Fatigue Severity Scale (FSS) scores was 39, with 87% sensitivity and 50% specificity (AUC = 0.725, 95% CI: 0.629 -0.820, p < 0.001). Joint use of FSS and PSQI scores increased the predictive value for sarcopenia(AUC = 0.804, 95% CI: 0.724-0.885, p < 0.001). CONCLUSION: Patients with PD are more susceptible to sarcopenia than healthy older adults, and fatigue and poorer sleep are positively associated with sarcopenia. Further longitudinal studies are needed to clarify the causal relationships.

Mental health, sleep quality, and hormonal circadian rhythms in pregnant women with threatened preterm labor: a prospective observational study.

BACKGROUND: Threatened preterm labor (TPL) is an important obstetrical challenge. Pregnant women with TPL may develop psychological and physical problems such as mental health disorders, sleep disturbance, and hormonal circadian rhythm disruption. This study aimed to investigate the current state of mental health, sleep quality, and circadian rhythms of cortisol and melatonin secretion in pregnant women with TPL and normal pregnant women (NPW). METHODS: A prospective observational clinical study was conducted at a maternal and child health hospital in Fuzhou, China, between June and July 2022. A total of 50 women between 32 and 36 weeks of gestation (TPL group, n = 20; NPW group, n = 30) were recruited. Data on anxiety symptom (Zung's Self-rating Anxiety Scale, SAS), depression symptom (Edinburgh Postnatal Depression Scale, EPDS), subjective sleep quality (Pittsburgh Sleep Quality Index, PSQI) and objective sleep outcomes (measured by actigraphy) of the pregnant women were collected at the time of enrolment. Salivary samples were collected once every 6 h (i.e., at 06:00, 12:00, 18:00, and 00:00) during 2 consecutive days to measure the circadian rhythm of hormone (cortisol and melatonin). RESULTS: There were no differences found in the total scores of SAS, EPDS scores, subjective sleep quality between the TPL and NPW groups (P > 0.05). In contrast, significant differences were found in sleep efficiency, total sleep time, wake time after sleep onset, and average awakening time between the groups (P < 0.05). The circadian rhythm of melatonin secretion was disrupted in the TPL group (P = 0.350); however, it was maintained in the NPW group (P = 0.044). The circadian rhythm of cortisol secretion was disrupted in both groups (P > 0.05). CONCLUSIONS: In the third trimester of pregnancy, women with TPL suffer from poorer sleep quality and disruption of circadian rhythm of melatonin secretion compared with NPW. Nevertheless, there were no differences found in mental health (i.e., anxiety and depression) and circadian rhythm of cortisol secretion. Large-scale studies should be conducted to evaluate these changes in women with TPL. TRIAL REGISTRATION: The study was registered from Chinese Clinical Trial Registry (Number: ChiCTR2200060674) on 07/06/2022.

Pregnane X receptor (PXR) deficiency protects against spinal cord injury by activating NRF2/HO-1 pathway.

INTRODUCTION: As a devastating neurological disease, spinal cord injury (SCI) results in severe tissue loss and neurological dysfunction. Pregnane X receptor (PXR) is a ligand-activated nuclear receptor with a major regulatory role in xenobiotic and endobiotic metabolism and recently has been implicated in the central nervous system. In the present study, we aimed to investigate the role and mechanism of PXR in SCI. METHODS: The clip-compressive SCI model was performed in male wild-type C57BL/6 (PXR+/+ ) and PXR-knockout (PXR-/- ) mice. The N2a H2 O2 -induced injury model mimicked the pathological process of SCI in vitro. Pregnenolone 16α-carbonitrile (PCN), a mouse-specific PXR agonist, was used to activate PXR in vivo and in vitro. The siRNA was applied to knock down the PXR expression in vitro. Transcriptome sequencing analysis was performed to discover the relevant mechanism, and the NRF2 inhibitor ML385 was used to validate the involvement of PXR in influencing the NRF2/HO-1 pathway in the SCI process. RESULTS: The expression of PXR decreased after SCI and reached a minimum on the third day. In vivo, PXR knockout significantly improved the motor function of mice after SCI, meanwhile, inhibited apoptosis, inflammation, and oxidative stress induced by SCI. On the contrary, activation of PXR by PCN negatively influenced the recovery of SCI. Mechanistically, transcriptome sequencing analysis revealed that PXR activation downregulated the mRNA level of heme oxygenase-1 (HO-1) after SCI. We further verified that PXR deficiency activated the NRF2/HO-1 pathway and PXR activation inhibited this pathway in vitro. CONCLUSION: PXR is involved in the recovery of motor function after SCI by regulating NRF2/HO-1 pathway.

Pregnane X receptor activation alleviates renal fibrosis in mice via interacting with p53 and inhibiting the Wnt7a/ß-catenin signaling.

Renal fibrosis is a common pathological feature of chronic kidney disease (CKD) with various etiologies, which seriously affects the structure and function of the kidney. Pregnane X receptor (PXR) is a member of the nuclear receptor superfamily and plays a critical role in regulating the genes related to xenobiotic and endobiotic metabolism in mammals. Previous studies show that PXR is expressed in the kidney and has protective effect against acute kidney injury (AKI). In this study, we investigated the role of PXR in CKD. Adenine diet-induced CKD (AD) model was established in wild-type and PXR humanized (hPXR) mice, respectively, which were treated with pregnenolone-16α-carbonitrile (PCN, 50 mg/kg, twice a week for 4 weeks) or rifampicin (RIF, 10 mg·kg-1·d-1, for 4 weeks). We showed that both PCN and RIF, which activated mouse and human PXR, respectively, improved renal function and attenuated renal fibrosis in the two types of AD mice. In addition, PCN treatment also alleviated renal fibrosis in unilateral ureter obstruction (UUO) mice. On the contrary, PXR gene deficiency exacerbated renal dysfunction and fibrosis in both adenine- and UUO-induced CKD mice. We found that PCN treatment suppressed the expression of the profibrotic Wnt7a and ß-catenin in AD mice and in cultured mouse renal tubular epithelial cells treated with TGFß1 in vitro. We demonstrated that PXR was colocalized and interacted with p53 in the nuclei of tubular epithelial cells. Overexpression of p53 increased the expression of Wnt7a, ß-catenin and its downstream gene fibronectin. We further revealed that p53 bound to the promoter of Wnt7a gene to increase its transcription and ß-catenin activation, leading to increased expression of the downstream profibrotic genes, which was inhibited by PXR. Taken together, PXR activation alleviates renal fibrosis in mice via interacting with p53 and inhibiting the Wnt7a/ß-catenin signaling pathway.

The dependent correlation between soil multifunctionality and bacterial community across different farmland soils.

Introduction: Microorganisms play a critical role in soil biogeochemical cycles, but it is still debated whether they influence soil biogeochemical processes through community composition and diversity or not. This study aims to investigate variation in bacterial community structure across different soils and its correlation to soil multifunctionality. Soil samples were collected from five typical farmland zones along distinct climatic gradients in China. Methods: The high-throughput sequencing (Illumina MiSeq) of 16S rRNA genes was employed to analyze bacterial community composition in each soil sample. Multivariate analysis was used to determine the difference in soil properties, microbial community and functioning, and their interactions. Results: Cluster and discrimination analysis indicated that bacterial community composition was similar in five tested soil samples, but bacterial richness combined with soil enzyme activities and potential nitrification rate (PNR) contributed most to the differentiations of soil samples. Mantel test analysis revealed that bacterial community composition and richness were more significantly shaped by soil nutrient conditions and edaphic variables than bacterial diversity. As for soil multifunctionality, soil microbial community level physiological profiles were little affected by abiotic and biotic factors, while soil enzymes and PNR were also significantly related to bacterial community composition and richness, in addition to soil N and P availability. Conclusion: Cumulatively, soil enzymes' activities and PNR were greatly dependent on bacterial community composition and richness not diversity, which in turn were greatly modified by soil N and P availability. Therefore, in the future it should be considered for the role of fertilization in the modification of bacterial community and the consequent control of nutrient cycling in soil.

Investigating the WNT/TCF pathway and the value of DCE-MRI in predicting and evaluating the efficacy of neoadjuvant radiotherapy and chemotherapy for locally advanced rectal cancer.

The purpose of this research was to Detach the DCE-MRI value in predicting and evaluating the efficacy of neoadjuvant radiotherapy and chemotherapy in middle and low locally advanced rectal cancer (READ). For this purpose, 40 patients with READ were examined by DCE-MRI and DWI before CRT treatment and 4 weeks after CRT treatment, and examined by Avanto1.5T magnetic resonance imaging scanner. According to the comparison of the postoperative pathological T stage and pre-nCRT T stage, the patients with decreased stage were defined as the T-descending group, and those with unchanged or elevated staging were defined as the T-undescending group. The ROC curve was used to evaluate the value of ADC value and Ktrans value to predict the early curative effect of neoadjuvant radiation therapy and chemotherapy for READ. Results showed that The ADC values of the two groups after nCRT were higher than those before nCRT (P<0.05). Compared with the pre-nCRT T-decline group and T-non-decline group, the Ktrans value of the pre-T-decline group was higher than that of the T-non-decline group (P<0.05), and the Ktrans value of both groups after the nCRT was higher than that before nCRT (P<0.05). The difference and the rate of ADC in the T-depression group were higher than in the T-undescending group (P<0.05). Taking the change rate of the ADC value 0.17 as the optimal threshold, the sensitivity and specificity of predicting the T-descending stage of patients with READ after neoadjuvant radiotherapy and chemotherapy were 72.69% and 75.84%, respectively (95%CI:0.608-0.954); taking the pre-nCRTKtrans value 1.18/min as the optimal threshold, the sensitivity and specificity to predict the T-descending stage of READ patients after neoadjuvant radiation therapy and chemotherapy was 78.65% and 80.47%, respectively (95%CI:0.637-0.971). There was no significant difference between the change rate of ADC value and the Ktrans value before nCRT in predicting the early efficacy of neoadjuvant radiotherapy and chemotherapy for READ. In conclusion, ADC value and Ktrans value can reflect the tissue structure changes of READ after neoadjuvant chemotherapy. It can be seen that the change rate of ADC value and pre-nCRTKtrans value can predict the early efficacy of neoadjuvant radiotherapy and chemotherapy for READ. The results showed that Axin2 and ß-catenin factors along with other factors such as APC and CKI proteins are effective at the molecular level along with other factors in the WNT/TCF signaling pathway. These agents start their activity in the cytoplasm and exert their final effect on the genes in the nucleus.

Parenting sense of competence among chinese parents of premature infants: a cross-sectional study.

BACKGROUND: Parenting sense of competence is not only indispensable to the wellbeing of the parents of premature infants, but is also pivotal to the overall development of these infants. This study examined the level of parenting sense of competence and its associated factors in Chinese parents of preterm infants. METHODS: This cross-sectional study was performed at a university teaching hospital in Fuzhou (China) from December 2021 to April 2022. Data were collected using the Parenting Sense of Competence Scale, Edinburgh Postnatal Depression Scale, Social Support Rating Scale, Parenting Care Knowledge Subscale, Parenting Care Skill Subscale, and a sociodemographic questionnaire. RESULTS: A total of 401 Chinese parents were included in the analysis. The average parenting sense of competence scale score was 70.93 ± 13.06. After controlling for demographic characteristics, parenting knowledge (ß = 0.149, P = 0.013), parenting skills (ß = 0.241, P < 0.001), social support (ß = 0.184, P < 0.001) and depression (ß = -0.272, P < 0.001), were significantly associated with the parenting sense of competence score, and explained 43.60% of the variance in this score. CONCLUSIONS: Chinese parents of preterm infants were found to have a moderate parenting sense of competence. This could be further improved through efforts aimed at reducing depressive symptoms and increasing parenting knowledge, parenting skills, and social support.

Epidemiological and Molecular Characteristics of bla NDM-1 and bla KPC-2 Co-Occurrence Carbapenem-Resistant Klebsiella pneumoniae.

Objective: Carbapenem-resistant Klebsiella pneumoniae (CRKP) has emerged and spread worldwide. It can usually cause a serious threat complicating treatment options in clinical settings. However, treatment options are limited. The present study investigates the prevalence and genetic characteristics of bla NDM-1 and bla KPC-2 co-harboring clinical isolates of Klebsiella pneumoniae. Methods: In this study, Multiplex polymerase chain reaction (PCR) was performed to detect the carbapenem-resistant genes, and the broth microdilution method was used to determine the minimum inhibitory concentrations (MICs) of antibacterial drugs. The transferability of carbapenem-resistant phenotypes was examined using filter mating assays. Overall, we used Illumina sequencing to evaluate the epidemiological and molecular characteristics of bla NDM-1 and bla KPC-2 (genes encoding carbapenemase) co-occurrence in CRKP strains. Results: All strains exhibited resistance to carbapenems and other antibiotics. However, they were still susceptible to polymyxin E. Among them, 18 isolates were positive for bla KPC-2, bla NDM-1, and multiple virulence determinants, such as genes encoding the virulence factor aerobactin, yersiniabactin, and the regulator of the mucoid phenotype (rmpA and rmpA2). Whole genome sequencing revealed that the 18 CRKP strains belonged to ST11 and capsular serotype KL64, and could be grouped into two evolutionary branches. Furthermore, these strains displayed hypervirulence potential since all of them carried pLVPK-like plasmid. Conclusion: These findings suggested that ST11-KL64 CRKP strains are major threats in terms of nosocomial infections in this hospital. Hence, new strategies should be urgently developed to monitor, diagnose, and treat this high-risk CRKP clone.