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Yurong Ou, Ningqi Wu, Lishan Shu, Yang Zhao, Yunfang Bao, Qiong Wu Department of Pathology, The First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui, People’s Republic of ChinaCorrespondence: Qiong Wu, Department of Pathology, The First Affiliated Hospital of Bengbu Medical University, 287, Changhuai Road, Bengbu, Anhui Province, People’s Republic of China, Tel +86-18607490054, Email wuqiong@bbmc.edu.cnBackground: Existing research shows inducing ferroptosis can improve the effectiveness of tumor treatment. Glutathione peroxidase 4 (GPX4) is a ferroptosis inhibitor. Solute carrier family 7, membrane 11 (SLC7A11) plays a key role in glutathione homeostasis, which is important for protecting cells from oxidative stress. β-catenin is the key protein the Wnt/β-catenin signaling pathway. The purpose of this study was to investigate the expression of SLC7A11 and GPX4 in colorectal cancer (CRC) and their relationship with β-catenin and to analyze the association of these two factors with several clinicopathological features and patient survival.Methods: This study retrospectively collected paraffin-embedded tissue samples from 120 CRC patients, who received surgical resection between 2017 and 2018. We examined the patterns of expression of SLC7A11, GPX4 and β-catenin by using immunohistochemistry. Analyzing the relationships between SLC7A11, GPX4, β-catenin and clinical pathological parameters and their relationships with overall survival (OS).Results: Expression of SLC7A11 and GPX4 were high expression in 60.83% and 64.17% among the patients, respectively, and were higher than those in normal tissue. SLC7A11, GPX4 and β-catenin were positively correlated with each other (P< 0.05). Expression of SLC7A11 and GPX4 significantly correlates with tumor stage and lymph node metastasis (P < 0.05). The β-catenin was related to lymph node metastasis, TNM stage and tumor grade. Kaplan–Meier analysis showed that patient’s OS in the SLC7A11 and GPX4 were reduced (P< 0.05). Univariate and multivariate analyses showed that SLC7A11 and GPX4 were independent risk factors for CRC prognosis.Conclusion: SLC7A11 and GPX4 overexpression is associated with β-catenin and poor prognosis and may be important for predicting CRC invasion, metastasis, and prognosis.Keywords: colorectal cancer, SLC7A11, GPX4, β-catenin, prognosis

Submarine groundwater discharge (SGD) contributes to the physical and chemical characters of coastal waters by discharging nutrients and contaminants, significantly impacting regional marine ecosystems and contributing to ocean chemical budgets. However, such groundwater discharge varies dramatically across scales and is often not comparable due to different model assumptions and field designs. We used a hydrologic model with integration of fundamental surface and subsurface processes to simulate the coastline level fresh SGD for the Crete Island in the Mediterranean Sea. The modeled hydrological processes suggested that fresh SGD substantially contributes to water flow entering the Mediterranean Sea (2.3 × 108 m3/yr), amounting to 31% of river discharge and 14% of precipitation. Spatially, fresh SGD varied from 2.4 m3/yr/m to 13.4 × 104 m3/yr/m, with an average of 2.6 × 103 m3/yr/m. The local maxima were commonly associated with river mouths reflecting larger hydraulic gradients and higher permeable structures. Temporally, fresh SGD was impacted by episodic precipitation in a delayed and prolonged pattern. We found that fresh SGD variability at the coastline segment level was compared to point measurements and fresh SGD magnitudes summered up to the catchment level were consistent with global products. Our results suggest the coupled surface–subsurface hydrologic modeling approach is a promising strategy to quantify and partition large-scale water budgets down to point observations that typically do not capture the full range of fresh SGD dynamics.

Xi-Qing Pan, Jin-Hui Liu, Jiang-Li Zhang, An Chai, Feng Li, Lei Shu, Wei Zhao Department of Joint Surgery, Third Hospital of Shijiazhuang, Shijiazhuang, Hebei, People’s Republic of ChinaCorrespondence: Jin-Hui Liu, Department of Joint Surgery, Third Hospital of Shijiazhuang, No. 15 Tiyu South Street, Shijiazhuang, Hebei, 050011, People’s Republic of China, Tel +86 13191872146, Fax +86 31185990628, Email jinhuiauliu6@126.comObjective: In this study, we aim to examine the effects of osteotomy under varying posterior slope angles on knee joint function recovery following knee arthroplasty.Methods: We conducted a retrospective analysis from September 2015 to September 2018 on 240 patients who underwent knee arthroplasty three years previously. The study participants were categorized based on changes in the angle of the posterior slope before and after surgery: Group 1, > 5°; Group 2, 3°– 5°; Group 3, 0°– 3°; Group 4, − 3°– 0°; Group 5, < − 3°. All participants were affected with knee osteoarthritis. The Knee Society Clinical Rating System (KSS) knee function score, Western Ontario and McMaster Universities Arthritis Index (WOMAC) knee function score, Visual Analogue Scale (VAS) pain score, and postoperative complications were measured 3 years after surgery.Results: The level of pain experienced by the patients decreased significantly than before, with pain scores ranging from 1.0– 3.0, and there was a statistical difference between groups (H = 93.400, P

Fissures and conduits are main void of karstic aquifer. Karst aquifers are highly vulnerable to contamination as water exchange between fissure system and conduit system greatly influences the karstification of limestone terrains, heterogeneity of karstic aquifer, and spring flow regime. A two-dimensional tank model was constructed, and a corresponding numerical model (MODFLOW-2005 Conduit Flow Process Mode 1, CFPM1) was developed to explore the effects of rainfall intensity and intrinsic structure of karst system (hydraulic conductivity of fissures and conduit diameter) on conduit-matrix water exchange. Nine different scenarios were designed to quantitatively simulate the spatial and temporal variability of water exchange between the fissures and conduits. The study reproduced the area of fissure water recharging to conduit (recharge zone), the area of conduit water discharging to fissure water (discharge zone) and the area of fissure water moving laterally (transport zone) in both physical model and numerical model. The results from rainfall scenarios show a relatively stable ratio of exchange zone (recharge zone and discharge zone) with increasing rainfall intensity, indicating that conduit-matrix water exchange is not sensitive to rainfall intensity, and conduit water discharging to fissure water is just a short-term phenomenon. It is also found that an increase in hydraulic conductivity of fissure system enhances extensiveness of water transport, but restrains conduit-matrix water exchange. However, the enlargement of conduit can prompt the extent of conduit-matrix water exchange. A positive feedback between the extent of conduit-matrix water exchanges and karstification can be confirmed. These findings might be essential for better understanding groundwater flow dynamics in karst aquifers.

We have measured the superconducting penetration depth Λ(T) in the heavy-fermion/intermediate-valent superconducting alloy series Ce1-xYbxCoIn5 using a transverse-field muon spin relaxation to study the effect of intermediate-valent Yb doping on Fermi-liquid renormalization. From Λ(T) we determine the superfluid density ρs(T) and find that it decreases continuously with increasing nominal Yb concentration x, i.e., with increasing intermediate valence. The temperature-dependent renormalization of the "normal" fluid density ρN(T)=ρs(0)-ρs(T) in both the heavy-fermion and intermediate valence limits is proportional to the temperature-dependent renormalization of the specific heat. This indicates that the temperature-dependent Fermi-liquid Landau parameters of the superconducting quasiparticles entering the two different physical quantities are the same. These results represent an important advance in understanding of both intermediate valence and heavy-fermion phenomena in superconductors.

Jinxia Wei,&ast; Simiao Fan,&ast; Hongxin Yu,&ast; Lexin Shu, Yubo Li School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yubo LiSchool of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, No. 10, Poyang Lake Road, West Zone, Tuanbo New City, Jinghai District, Tianjin, 301617, People’s Republic of ChinaTel +86-22-59591974Email yaowufenxi001@sina.comBackground: The interaction of small molecules with direct targets constitutes the molecular initiation events of drug efficacy and toxicity. Aconitine, an active compound of the Aconitum species, has various pharmacological effects but is strongly toxic to the heart. The direct targets of aconitine-induced cardiotoxicity remain unclear.Methods: We predicted the toxic targets of aconitine based on network pharmacology and followed a novel proteomic approach based on the “drug affinity responsive target stability” technology combined with LC-MS/MS to identify the direct targets of aconitine. The identified targets were analysed from the perspective of multilevel and multidimensional bioinformatics through a network integration method. The binding sites were investigated via molecular docking to explore the toxicity mechanism and predict the direct targets of aconitine. Finally, atomic force microscopy (AFM) imaging was performed to verify the affinity of aconitine to the direct targets.Results: PTGS2, predicted by network pharmacology as a toxic target, encodes cyclooxygenase 2 (COX-2), which is closely related to myocardial injury. Furthermore, cytosolic phospholipase A2 (cPLA2) is the upstream signal protein of PTGS2, and it is a key enzyme in the metabolism of arachidonic acid during an inflammatory response. We determined cPLA2 as a direct target, and AFM imaging verified that aconitine could bind to cPLA2 well; thus, aconitine may cause the expression of PTGS2/COX-2 and release inflammatory factors, thereby promoting myocardial injury and dysfunction.Conclusion: We developed a complete set of methods to predict and verify the direct targets of aconitine, and cPLA2 was identified as one. Overall, the novel strategy provides new insights into the discovery of direct targets and the molecular mechanism of toxic components that are found in traditional Chinese medicine.Keywords: aconitine, cardiotoxicity, direct targets, drug affinity responsive target stability technology, atomic force microscopy

Zhilan Yao,1,2 Liuping Shu,1,2 Yi Yi,1,2 Lifu Qiao1,2 1Department of Gynecology, Wujin Hospital Affiliated with Jiangsu University, Changzhou, Jiangsu Province, 213100, People’s Republic of China; 2Department of Gynecology, The Wujin Clinical College of Xuzhou Medical University, Changzhou, Jiangsu Province, 213100, People’s Republic of ChinaCorrespondence: Yi Yi; Lifu QiaoDepartment of Gynecology, Wujin Hospital Affiliated with Jiangsu University, No. 2 Yongning North Road, Changzhou, Jiangsu Province, 213100, People’s Republic of ChinaTel +86-0519-85336190Email dryiyi_wj@126.com; guanhangej290@163.comAim: Cervical cancer (CC) is the fourth most common cancer among women worldwide. We aimed to explore the role of hsa_circ_000543 played in CC.Methods: The hsa_circ_000543 expressions in CC tissues and cells were measured by qRT-PCR. The correlation of hsa_circ_000543 expression and the clinical features of CC patients were analyzed by SPSS 20.0. The up- or down-regulated plasmids of hsa_circ_000543 were respectively transfected into CC cells. Cell proliferation, apoptosis and colony formation were detected through CCK-8 assay, flow cytometry and cell colony formation assay, respectively. The cell migration and invasion were evaluated by Transwell assay. The underlying molecular mechanism of hsa_circ_000543 was studied by bioinformatic prediction tools and luciferase reporter assay. Rescue experiments were performed to validate the regulation mechanism of hsa_circ_000543/miR-567/ZNF268 axis in CC.Results: Hsa_circ_000543 was over-expressed in CC tissues and cells. The high expression of hsa_circ_000543 indicated poor prognosis of CC patients. Hsa_circ_000543 promoted cell proliferation, colony formation, migration and invasion, as well as inhibited cell apoptosis in CC cells. Hsa_circ_000543 directly targeted miR-567/ZNF268 in CC cell lines. In CC tumor tissues and cells, the hsa_circ_000543 expression was negatively correlated with miR-567 expression and showed a positive correlation with ZNF268 expression. The rescue experiments revealed that hsa_circ_000543 mediated cell proliferation, apoptosis, colony formation, migration and invasion of CC cells via regulating miR-567/ZNF268 axis.Conclusion: Hsa_circ_000543 regulated CC cell activities through binding miR-567 and therefore enhancing ZNF268 expression.Keywords: cervical cancer, circular RNA, hsa_circ_000543, miR-567, ZNF268

Type 2 diabetes (T2D) is characterized by insulin resistance and impaired insulin secretion, but the mechanisms underlying insulin secretion failure are not completely understood. Here, we show that a set of co-expressed genes, which is enriched for genes with islet-selective open chromatin, is associated with T2D. These genes are perturbed in T2D and have a similar expression pattern to that of dedifferentiated islets. We identify Sox5 as a regulator of the module. Sox5 knockdown induces gene expression changes similar to those observed in T2D and diabetic animals and has profound effects on insulin secretion, including reduced depolarization-evoked Ca2+-influx and β-cell exocytosis. SOX5 overexpression reverses the expression perturbations observed in a mouse model of T2D, increases the expression of key β-cell genes and improves glucose-stimulated insulin secretion in human islets from donors with T2D. We suggest that human islets in T2D display changes reminiscent of dedifferentiation and highlight SOX5 as a regulator of β-cell phenotype and function.

Xingran Du,1,* Jianpeng Xue,2,* Mingzi Jiang,3 Shaoqing Lin,4 Yuzhen Huang,4 Kaili Deng,5 Lei Shu,5 Hanmei Xu,2 Zeqing Li,2 Jing Yao,4 Sixia Chen,4 Ziyan Shen,4 Ganzhu Feng4 1Department of Infectious Disease, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 2State Key Laboratory of Natural Medicines, The Engineering Research Center of Synthetic Polypeptide Discovery and Evaluation of Jiangsu Province, China Pharmaceutical University, Nanjing, Jiangsu, People’s Republic of China; 3Department of Respiratory and Critical Care Medicine, The First People’s Hospital of Kunshan, Suzhou, Jiangsu, People’s Republic of China; 4Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 5Department of Respiratory Medicine, Sir Run Run Hospital, Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ganzhu FengDepartment of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of ChinaTel +86-025-58509837Fax +86-025-58509994Email zhu1635253@163.comBackground: The development of vaccines is a promising and cost-effective strategy to prevent emerging multidrug-resistant (MDR) Acinetobacter baumannii (A. baumannii) infections. The purpose of this study was to prepare a multiepitope peptide nanovaccine and evaluate its immunogenicity and protective effect in BALB/c mice.Methods: The B-cell and T-cell epitopes of Omp22 from A. baumannii were predicted using bioinformatics methods and identified by immunological experiments. The optimal epitopes were conjugated in series by 6-aminocaproic acid and chemically synthesized multiepitope polypeptide rOmp22. Then, rOmp22 was encapsulated by chitosan (CS) and poly (lactic-co-glycolic) acid (PLGA) to prepare CS-PLGA-rOmp22 nanoparticles (NPs). The immunogenicity and immunoprotective efficacy of the vaccine were evaluated in BALB/c mice.Results: CS-PLGA-rOmp22 NPs were small (mean size of 272.83 nm) with apparently spherical structures, positively charged (4.39 mV) and nontoxic to A549 cells. A high encapsulation efficiency (54.94%) and a continuous slow release pattern were achieved. Compared with nonencapsulated rOmp22, CS-PLGA-rOmp22 immunized BALB/c mice induced higher levels of rOmp22-specific IgG in serum and IFN-γ in splenocyte supernatant. Additionally, lung injury and bacterial burdens in the lung and blood were suppressed, and potent protection (57.14%-83.3%) against acute lethal intratracheal A. baumannii challenge was observed in BALB/c mice vaccinated with CS-PLGA-rOmp22.Conclusion: CS-PLGA-rOmp22 NPs elicited specific IgG antibodies, Th1 cellular immunity and protection against acute lethal intratracheal A. baumannii challenge. Our results indicate that this nanovaccine is a desirable candidate for preventing A. baumannii infection.Keywords: A. baumannii, epitope vaccine, polymeric nanoparticles, PLGA, chitosan

Linyi Shu, 1, 2 Hang Zhao, 2 Wenli Huang, 1, 2 Guangsen Hou, 1, 2 Guangyao Song, 1, 2 Huijuan Ma 1–3 1Department of Internal Medicine, Hebei Medical University, Shijiazhuang, Hebei 050017, People’s Republic of China; 2Endocrinology Department, Hebei General Hospital, Shijiazhuang, Hebei 050051, People’s Republic of China; 3Hebei Key Laboratory of Metabolic Diseases, Hebei General Hospital, Shijiazhuang, Hebei 050051, People’s Republic of ChinaCorrespondence: Guangyao SongEndocrinology Department, Hebei General Hospital, 348, Heping West Road, Shijiazhuang, Hebei 050051, People’s Republic of ChinaTel +86 311 8598 8556Email guangyaosong123@163.comPurpose: This study aimed to investigate how resveratrol (RSV) improves high-fat diet (HFD)-induced hepatic insulin resistance in mice via microRNA (miRNA) mmu-miR-363-3p in vitro and in vivo.Materials and Methods: C57BL/6J mice were fed a HFD for 8 weeks to establish an insulin resistance model. The model mice were treated or not with RSV for 6 weeks. Differential miRNA expression in mouse liver tissues was analyzed by high-throughput sequencing. Mouse HepG2 cells were treated with palmitic acid (PA) to establish a cell model of insulin resistance. HepG2 cells were transfected with mmu-miR-363-3p inhibitor or mimic, and the expression of PI3K-Akt signaling pathway-related proteins was analyzed.Results: Based on the high-throughput sequencing analysis, mmu-miR-363-3p was identified as a major miRNA involved in the action of RSV on insulin resistance. Based on KEGG pathway enrichment analysis, PI3K-Akt signaling was found to be significantly enriched among differentially expressed miRNAs, and this pathway is closely related to insulin resistance. RSV treatment reduced the expression of FOXO1 and G6PC, which are downstream of the PI3K-Akt pathway. In the cell model, mmu-miR-363-3p inhibitor significantly suppressed p-Akt and p-PI3K levels, but enhanced those of FOXO1 and G6PC. In contrast, mmu-miR-363-3p mimic significantly enhanced the p-Akt and p-PI3K levels, but suppressed FOXO1 and G6PC expression, which was similar to the effect of RSV.Conclusion: RSV improves insulin resistance by upregulating miRNA mmu-miR-363-3p via the PI3K-Akt pathway.Keywords: insulin resistance, resveratrol, microRNA, high-throughput sequencing, PI3K-Akt pathway

Hang Zhao,1 Linyi Shu,2 Wenli Huang,2 Wenzhao Wang,2 Guangyao Song1 1Endocrinology Department, Hebei General Hospital, Shijiazhuang, Hebei 050051, People’s Republic of China; 2Department of Internal Medicine, Hebei Medical University, Shijiazhuang, Hebei 050017, People’s Republic of ChinaCorrespondence: Guangyao SongEndocrinology Department, Hebei General Hospital, 348 Heping West Road, Shijiazhuang, Hebei 050051, People’s Republic of ChinaTel +86 311 85988556Email guangyaosong123@163.comIntroduction: Despite the increasingly young age at diabetes onset and the increasing number of deaths caused by type 2 diabetes mellitus (T2DM), why some patients develop macrovascular complications but others develop microvascular complications remains controversial and unclear. Notably, some patients have good glucose control but still develop vascular complications, whereas some patients have retinopathy with neither nephropathy nor neuropathy. This study will be performed to explore the risk factors for T2DM complications in Chinese patients.Methods and analysis: Patients with T2DM and healthy people will be recruited from Hebei General Hospital from September 2019 to September 2020. The subjects will be grouped into a control group, T2DM without vascular complications group, T2DM with macrovascular complications group, and T2DM with microvascular complications group; they will then be further subgrouped. The following data will be collected after admission: demographic information such as age, sex, and education; relevant medical history such as duration of diabetes, family history of first-degree relatives with diabetes, and age at diagnosis of diabetes; and anthropometric and blood indicators such as weight, waist circumference, fasting blood glucose level, C-peptide level, total cholesterol level, and triglyceride level. The statistical analysis will be performed using SPSS 22.0 (IBM Corp., Armonk, NY, USA). A P value of

Hang Zhao,1,2 Yunjia Zhang,1 Linyi Shu,1,2 Guangyao Song,1,2 Huijuan Ma1–31Department of Internal Medicine, Hebei Medical University, Shijiazhuang, Hebei 050017, People’s Republic of China; 2Endocrinology Department, Hebei General Hospital, Shijiazhuang, Hebei 050051, People’s Republic of China; 3Hebei Key Laboratory of Metabolic Diseases, Hebei General Hospital, Shijiazhuang, Hebei 050051, People’s Republic of ChinaPurpose: The aim of the study was to examine the effects of resveratrol upon hepatic endoplasmic reticulum stress (ERS) and insulin sensitivity in vivo and in vitro.Material and methods: C57BL/6J mice were fed a high-fat diet (HFD) for 8 weeks, and insulin resistance was evaluated by the intraperitoneal glucose tolerance test (IPGTT). Mice were then treated with resveratrol for 12 weeks and blood and liver samples collected. Blood biochemical indicators were determined by kits, liver protein expression was determined by western blot, and morphological changes were observed by histological staining. Palmitic acid (PA)-induced insulin-resistant HepG2 cells were established. Cells were exposed to 100, 50 or 20 μM resveratrol for 24 hrs, and proliferation/cytotoxicity was determined. Cells were divided into five groups: control, PA, PA + Rev (100 μM), PA + Rev (50 μM) and PA + Rev (20 μM) groups. After 24 hrs of treatment, cellular proteins were analyzed the same way as animal tissues.Results: The IPGTT confirmed that the insulin resistance model was established successfully. After resveratrol treatment, fasting blood glucose and cholesterol levels declined and the quantitative insulin sensitivity check index increased. Western-blot results showed that resveratrol-treated HFD mice had reduced hepatic levels of p-PERK, ATF-4 and TRIB3, and increased the levels of ATF-6, p-AKT and p-GSK3β. In the cell model, resveratrol with 100 and 50 μM enhanced ERS and insulin resistance, whereas 20 μM had beneficial effects, similar to the animal model.Conclusion: Resveratrol reduced hepatic ERS, thereby improving insulin sensitivity and glucose levels. However, high doses of resveratrol had harmful effects on cells, elevating ERS and insulin resistance. The safe dose of resveratrol needs further investigation.Keywords: blood glucose, insulin resistance, endoplasmic reticulum stress, resveratrol

Ling-bin Shu,1,* Qun Lu,2,* Ren-hua Sun,3 Le-qing Lin,4 Qiao-ling Sun,1 Jie Hu,1 Hong-wei Zhou,1 Edward Wai-Chi Chan,5,6 Sheng Chen,5,6 Rong Zhang11Department of Clinical Laboratory Medicine, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China; 2Department of Hospital Infection Management, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China; 3Department of Critical Care Medicine, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou, China; 4Department of Intensive Care Unit, The Affiliated Hospital of Hangzhou Normal University, Hangzhou, China; 5Shenzhen Key Lab for Food Biological Safety Control, Food Safety and Technology Research Center, Hong Kong PolyU Shen Zhen Research Institute, Shenzhen, China; 6State Key Lab of Chirosciences, Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong *These authors contributed equally to this work Objective: To understand the prevalence and transmission of carbapenem-resistant Klebsiella pneumoniae (CRKP) in ICU patients in Zhejiang Province, China, and determined the genetic and phenotypic characteristics of these CRKP strains. Materials and Methods: A total of 202 ICU patients from eight tertiary hospitals were recruited and 55 non-duplicate CRKP strains were collected during July and August in 2017. These strains were subjected to determination of MICs, carriage of carbapenemase genes and tet(A) variants, PFGE, MLST and virulence potential using G. mellonella larvae infection model. Results: A total of 55 CRKP strains were recovered from 42 patients, representing a carriage rate of 20.8%. CRKP strains were recovered from both the intestinal and respiratory tract of 13 patients. Importantly, strains isolated from sputum and fecal samples often displayed identical PFGE profiles, suggesting that CRKP may also colonize the respiratory tract. The most dominant ST type of these CRKP strains was ST11, accounting for 78% (43/55) of the test strains. The majority of CRKP strains were resistant to multiple antibiotics, with the exception of tigecycline and ceftazidime/avibactam. Interestingly, 32 strains were found to harbor the tet(A) variant, which is known to confer reduced tigecycline susceptibility. Assessment of the virulence potential of these CRKP strains by string test showed that results were negative for 53 of the 55 test strains. However, further assessment of virulence potential using a G. mellonella larvae infection model showed that CRKP isolated from sputum consistently exhibited a higher virulence level than strains recovered from fecal samples. Conclusion: CRKP is highly prevalent in ICU patients in Zhejiang Province with strains isolated from respiratory exhibiting higher virulence potential than those from GI tract. These data provide essential insight into development of new infection control measures to halt the transmission of CRKP in clinical settings. Keywords: carbapenem-resistant Klebsiella pneumoniae, surveillance, sputum, feces, ICU, resistance, virulence