Grid2 interacting protein is a potential biomarker related to immune infiltration in colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is one of the three deadliest malignant tumors in the world, posing a severe hazard to human health. Nonetheless, the 5-year survival rate for advanced CRC remains unsatisfactory. Grid2 interacting protein (GRID2IP) is a Purkinje fiber postsynaptic scaffold protein implicated in a number of signal transduction pathways in the nervous system. Previous studies have shown that Grid2 is closely related to the occurrence and prognosis of gastric cancer and many other diseases. Therefore, we aim to identify the relationship between GRID2IP and the occurrence and prognosis of CRC. METHODS: Transcriptome data were retrieved from The Cancer Genome Atlas (TCGA) database to analyze the differential expression of GRID2IP in a variety of malignant tumors and then validate it by quantitative real time polymerase chain reaction(Q-PCR) and Western Blot in HT29 and SW480 cells. "DESeq2" package was used to analyze the differentially expressed genes (DEGs) between the high- and low-GRID2IP subgroups. In relation to DEGs, Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed. In addition, gene set enrichment analysis (GSEA) and single-sample gene set enrichment analysis (ssGSEA) were employed to examine DEGs-associated signaling pathways and GRID2IP-associated immune cell infiltration levels. Besides, overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI) were compared between the two subgroups using a Kaplan-Meier analysis. In addition, a prognostic model for GRID2IP and clinical characteristics was developed using the univariate Cox regression method. The "pRRophetic" package was applied to predict the drug sensitivity of different subgroups. Moreover, we also performed single-cell analysis of GRID2IP using the TISCH database. RESULTS: GRID2IP is upregulated in CRC patients. The rise of GRID2IP inhibits the invasion of tumor-associated immune cells resulting in a lower immune score. In addition, high GRID2IP expression was associated with poor prognosis in different clinical subgroups. Analysis of single cells revealed that GRID2IP was predominantly expressed in immune cells, myofibroblasts, and cancerous cells. In terms of chemotherapy drug sensitivity, the subgroup with high GRID2IP expression was less sensitive to gemcitabine. CONCLUSIONS: Our results suggest that rising GRID2IP promotes tumor-associated immune cell infiltration and suggests adverse outcomes in CRC patients, which may be a useful biomarker for determining the prognosis of CRC and a potential target molecule for CRC therapy.

USP39 Regulates NF-κB-Mediated Inflammatory Responses through Deubiquitinating K48-Linked IκBα.

IκBα is a critical protein that inhibits NF-κB nuclear translocation and impairs NF-κB-mediated signaling. The abundance of IκBα determines the activation and restoration of the inflammatory response. However, posttranslational regulation of IκBα remains to be fully understood. In this study, we identified ubiquitin-specific protease 39 (USP39) as a negative regulator in the NF-κB inflammatory response by stabilizing basal IκBα. The expression of USP39 in macrophages was reduced under LPS-induced inflammation. Knockdown or knockout of USP39 in macrophages significantly increased the expression and secretion of proinflammatory cytokines upon exposure to LPS or Escherichia coli, whereas reexpression of exogenous USP39 in USP39-deficient macrophages rescued the effect. Moreover, USP39-defective mice were more sensitive to LPS or E. coli-induced systemic sepsis. Mechanistically, USP39 interacted with and stabilized IκBα by reducing K48-linked polyubiquination of IκBα. Taken together, to our knowledge, our study for the first time revealed the inhibitory function of USP39 in the NF-κB inflammatory response, providing a previously unknown mechanism for control of inflammatory cytokine induction in the cellular anti-inflammatory response.

USP22 suppresses the NLRP3 inflammasome by degrading NLRP3 via ATG5-dependent autophagy.

The NLRP3 inflammasome is involved in a diverse range of inflammatory diseases. The activation of inflammasomes must be tightly regulated to prevent excessive inflammation, and the protein ubiquitination system is reported to be one of the ways in which inflammasome activation is regulated. However, the deubiquitination regulatory mechanisms of inflammasome activation remain elusive. Here, we demonstrated that USP22 (ubiquitin specific peptidase 22) promotes NLRP3 degradation and inhibits NLRP3 inflammasome activation. USP22 deficiency or in vivo silencing significantly increases alum-induced peritonitis and lipopolysaccharide-induced systemic inflammation. Mechanistically, USP22 inhibits NLRP3 inflammasome activation via the promotion of ATG5-mediated macroautophagy/autophagy. USP22 stabilizes ATG5 via decreasing K27- and K48-linked ubiquitination of ATG5 at the Lys118 site. Taken together, these findings reveal the role USP22 plays in the regulation of NLRP3 inflammasome activation and suggest a potential therapeutic target to treat NLRP3 inflammasome-related diseases.Abbreviations: ATG5: autophagy related 5; ATP: adenosine triphosphate; CASP1: caspase 1; IL18: interleukin 18; IL1B/IL-1ß: interleukin 1 beta; LPS: lipopolysaccharide; NLRC4: NLR family, CARD domain containing 4; NLRP3: NLR family, pyrin domain containing 3; PYCARD/ASC: PYD and CARD domain containing; TNF/TNF-α: tumor necrosis factor; USP22: ubiquitin specific peptidase 22.

The evaluation of fecal microbiota transplantation vs vancomycin in a Clostridioides difficile infection model.

Vancomycin is the preferred treatment for Clostridioides difficile infection (CDI) but has been associated with a high recurrence rate of CDI in treated patients. Fecal microbiota transplantation (FMT) has emerged as a remarkably successful treatment for recurrent CDI (rCDI). Herein, we present a mouse model of CDI to further define the changes in intestinal inflammation, flora, and metabolites following FMT versus vancomycin treatment and to find the potential therapy to restore colonization resistance. Both FMT and vancomycin treatment could ameliorate CDI-induced clinical features and intestinal tissue damage, with decrease in the levels of inflammatory mediators like IL-1ß, IL-6, TNF-α, G-CSF, and MCP-1 in the colon and plasma. Observing the fecal gut microbiome profile revealed that unlike vancomycin, FMT could replenish intestinal microbiota by augmenting the relative abundance of the phylum Bacteroidetes and eliminating the abundance of the phylum Proteobacteria. FMT also reduced the levels of several carbohydrates, such as raffinose and fructose-6-phosphate, and amino acids, including tryptophan and glutamyl-valine, in the gut metabolome, thus suppressing C. difficile germination and growth. Our results suggest that the FMT-induced reconstruction of a specific gut community structure and restoration of metabolites promote the recovery of colonization resistance in mice better than vancomycin, thus offering new insights for the prevention of rCDI. KEY POINTS: • Both FMT and vancomycin ameliorate CDI-induced inflammatory response. • FMT restores a specific community structure and gut metabolites. • Mice treated with FMT may promote the recovery of colonization resistance and has a better outcome.

HDAC11 negatively regulates antifungal immunity by inhibiting Nos2 expression via binding with transcriptional repressor STAT3.

Fungal infections cause serious health problems, especially in patients with an immune-deficiency. Histone deacetylase 11 (HDAC11) mediates various immune functions, yet little is known about its role in regulating host immune responses to fungal infection. Here we report that HDAC11 negatively controls antifungal immunity in macrophages and dendritic cells. Deleting Hdac11 protects mice from morbidity and markedly improves their survival rate upon systemic infection with Candida albicans (C. albicans). Moreover, HDAC11 deficiency results in increased production of NO and reactive oxygen species, which enhances fungal killing. Mechanistically, loss of HDAC11 increases histone 3 and 4 acetylation at the Nos2 promoter and leads to enhanced Nos2 transcription and corresponding iNOS levels in macrophages. In addition, STAT3, a transcriptional repressor of Nos2, physically interacts with HDAC11, serving as a scaffold protein supporting the HDAC11 association with the Nos2 promoter. Notably, treatment with the HDAC11 inhibitor, FT895, exhibits antifungal therapeutic effects in both mouse and human cells challenged with C. albicans. These data support that HDAC11 may be a therapeutic target for fungal infection.

Munronoid I Ameliorates DSS-Induced Mouse Colitis by Inhibiting NLRP3 Inflammasome Activation and Pyroptosis Via Modulation of NLRP3.

Inflammatory bowel diseases (IBDs) are increasingly common diseases characterized by chronic and relapsing inflammation of the gastrointestinal tract. NLRP3 might be a crucial regulator of the homeostatic balance of the intestine, but its upregulation leads to pyroptosis. Munronoid I is extracted and purified from Munronia sinica, which has shown an anti-inflammatory effect, but the efficacy of Munronoid I in IBD remains unproven. In this study, we attempted to determine the effect of Munronoid I on NLRP3 to regulate the inflammasome activation and pyroptosis in IBD. Our data demonstrated that Munronoid I treatment attenuated DSS-induced body weight loss, pathological injury of the colon, the production of IL-1ß and IL-18, and the expression of pyroptosis-associated proteins in colon tissue in mice. Moreover, Munronoid I inhibited LPS/ATP-induced pyroptosis in mouse peritoneal macrophages, MODE-K cells, and DSS-induced pyroptosis in mouse colonic epithelial cells, and decreased the release of inflammatory cytokines IL-1ß and IL-18 in mouse peritoneal macrophages. Mechanically, Munronoid I could suppress the NLRP3 inflammasome activation and pyroptosis by promoting the K48-linked ubiquitination and NLRP3 degradation. It is suggested that Munronoid I might be a potential therapeutic candidate for IBD.

Succinate Is a Natural Suppressor of Antiviral Immune Response by Targeting MAVS.

Succinate is at the crossroads of multiple metabolic pathways and plays a role in several immune responses acting as an inflammation signal. However, whether succinate regulates antiviral immune response remains unclear. Here, we found that the production of succinate was reduced in RAW264.7 cells during vesicular stomatitis virus (VSV) infection. Using diethyl succinate to pretreat the mouse peritoneal macrophages and RAW264.7 cells before VSV infection, the production of interferon-ß (IFN-ß), chemokine (C-X-C motif) ligand 10 (CXCL-10), and IFN-stimulated genes 15 (ISG15) was significantly decreased, following which the VSV replication in diethyl succinate-pretreated cells was obviously increased. Moreover, succinate decreased the expression of IFN-ß in serum, lung, and spleen derived from the VSV-infected mice. The overall survival rate in the VSV-infected mice with diethyl succinate pretreatment was also remarkably downregulated. Furthermore, we identified that succinate inhibited the activation of MAVS-TBK1-IRF3 signaling by suppressing the formation of MAVS aggregates. Our findings provide previously unrecognized roles of succinate in antiviral immune response and establish a novel link between metabolism and innate immune response.

TfR-T12 short peptide and pH sensitive cell transmembrane peptide modified nano-composite micelles for glioma treatment via remodeling tumor microenvironment.

Two kinds of amphiphilic block copolymers of TfR-T12-PEG-PLGA and TATH7-PEG-PLGA were synthesized to self-assembly nano-composite micelles for encapsulating paclitaxel and imiquimod synchronously. TfR-T12 peptide modified nano-composite micelles can pass through BBB in a TfR-mediated way to achieve targeted delivery of chemotherapeutic drugs, and pH sensitive TATH7 peptide modified nano-composite micelles enhanced uptake efficiency more significantly under pH 5.5 medium than pH 7.4 medium. The results of pharmacodynamic evaluation in vivo showed that the nano-composite micelles had achieved good anti-tumor effect in subcutaneous and normotopia glioma models, and effectively prolonged the life cycle of tumor-bearing mice. The nano-composite micelles regulated the immunosuppression phenomenon of tumor microenvironment significantly, and promoted the M1 polarization of TAMs, then enhanced the proliferation and activation of CD8+ T cells in tumor microenvironment. It comes to conclusion that the nano-composite micelle achieves the purpose of effective treatment of glioma by chemotherapy combined with immunotherapy.

MEF2C promotes M1 macrophage polarization and Th1 responses.

The polarization of macrophages to the M1 or M2 phenotype has a pivotal role in inflammation and host defense; however, the underlying molecular mechanism remains unclear. Here, we show that myocyte enhancer factor 2 C (MEF2C) is essential for regulating M1 macrophage polarization in response to infection and inflammation. Global gene expression analysis demonstrated that MEF2C deficiency in macrophages downregulated the expression of M1 phenotypic markers and upregulated the expression of M2 phenotypic markers. MEF2C significantly promoted the expression of interleukin-12 p35 subunit (Il12a) and interleukin-12 p40 subunit (Il12b). Myeloid-specific Mef2c-knockout mice showed reduced IL-12 production and impaired Th1 responses, which led to susceptibility to Listeria monocytogenes infection and protected against DSS-induced IBD in vivo. Mechanistically, we showed that MEF2C directly activated the transcription of Il12a and Il12b. These findings reveal a new function of MEF2C in macrophage polarization and Th1 responses and identify MEF2C as a potential target for therapeutic intervention in inflammatory and autoimmune diseases.

Indole derivative XCR-5a alleviates LPS-induced inflammation in vitro and in vivo.

CONTEXT: Few studies on anti-inflammatory drugs with indole groups have been published. This is the first study that demonstrates the anti-inflammatory effects of indole derivative XCR-5a in vitro and in vivo. OBJECTIVE: This study aimed to discover more anti-inflammatory drugs with indole groups and investigate their anti-inflammatory mechanisms. MATERIALS AND METHODS: First, a series of indole derivatives was synthesized, then screened for XCR-5a, a compound with anti-inflammatory effects. Second, the in vitro production of IL-1ß, IL-6, TNF-α, inducible nitric oxide synthase (iNOS), and cyclo-oxygenase-2 (COX-2) in lipopolysaccharide (LPS)-induced primary cells of mice pretreated with XCR-5a was determined using qPCR and ELISA. Finally, the effect of XCR-5a on LPS-induced NF-κB signaling activation was determined by Western blotting. An in vivo mouse sepsis model was established. In mouse lung tissue, the production of IL-1ß, IL-6, and TNF-α was determined and H&E staining was performed. RESULTS: Our findings showed that XCR-5a could suppress the production of LPS-induced IL-1ß, IL-6, and TNF-α, as well as mRNA expression of iNOS and COX-2. Pretreatment with XCR-5a inhibited the LPS-induced inflammatory response in septic mice in vivo by decreasing pro-inflammatory cytokines production in serum and reducing immune cell infiltration. Mechanistically, XCR-5a suppressed LPS-induced activation of the NF-κB signaling pathway. CONCLUSIONS: XCR-5a has anti-inflammatory effects in vitro and in vivo. Therefore, XCR-5a could be a potential drug candidate for the treatment of inflammatory diseases.

Synthesis compound XCR-7a ameliorates LPS-induced inflammatory response by inhibiting the phosphorylation of c-Fos.

Inflammation is a biological process closely related to different kinds of diseases, such as cancer and metabolic diseases. Therefore, effective control of the occurrence and development of inflammation is of great significance for disease prevention and control. Recently, 2-substituted indoles have gradually become a research hotspot because of their stability and pharmacological activity. Here we synthesized a series of compound containing 2-substituted indoles and investigated XCR-7a's role in inflammatory response. Our data show that XCR-7a can inhibit the production of inflammatory cytokines interleukin-1 beta (IL-1ß), interleukin-6 (IL-6) and inflammatory mediator cyclooxygenase-2 (COX-2) induced by lipopolysaccharide (LPS) in mouse peritoneal macrophages. Also, XCR-7a has a protective effect on LPS-induced inflammatory response in mice. Mechanically, we found that XCR-7a could inhibit the phosphorylation of c-Fos induced by LPS, which suggested that the protective effect of XCR-7a on inflammation was related to its negative regulation to phosphorylation of c-Fos. Briefly, our results demonstrated that XCR-7a could be expected to be a potential drug for controlling inflammation.

USP19 (ubiquitin specific peptidase 19) promotes TBK1 (TANK-binding kinase 1) degradation via chaperone-mediated autophagy.

TBK1 (TANK-binding kinase 1) is an essential receptor protein required for the innate immune response, but the mechanisms underlying TBK1 stability, especially those regulated via autophagy, remain poorly understood. Here, we demonstrate that USP19 (ubiquitin specific peptidase 19) interacts with and promotes TBK1 lysosomal degradation via chaperone-mediated autophagy (CMA). We observed that TBK1 had a canonical CMA motif, knocking down key proteins involved in CMA (HSPA8/HSC70 or LAMP2A) or inhibiting CMA-prevented USP19-mediated TBK1 degradation. Furthermore, USP19 deficiency in macrophages caused an elevation of TBK1 and the activation of the type-I interferon signaling pathway after vesicular stomatitis virus (VSV) infection. Consistently, macrophage-specific usp19 knockout in mice resulted in attenuated VSV replication and resistance to VSV infection in vivo. Altogether, our results suggest that USP19 is a key regulator of TBK1 and uncovers a previously uncharacterized role for USP19 in CMA-mediated TBK1 degradation and infectious diseases.

Natural molecule Munronoid I attenuates LPS-induced acute lung injury by promoting the K48-linked ubiquitination and degradation of TAK1.

Acute lung injury (ALI) is a severe lung disease with limited therapeutic strategies. Munronoid I, a limonoid, which is extracted and purified from Munronia sinica, exhibits effective anti-neoplastic activities. In this study, we attempted to determine the anti-inflammatory effects of Munronoid I using both the lipopolysaccharide (LPS)-induced in vivo murine ALI models and in vitro assays. Our results demonstrated that Munronoid I treatment ameliorated LPS-induced ALI and inflammation in mice. Moreover, it also significantly inhibited LPS-induced pathological injuries, infiltration of inflammatory cells, and production of IL-1ß and IL-6. Furthermore, the in vitro assay showed that Munronoid I could inhibit the LPS-induced expression of inflammatory mediators such as iNOS, COX2, and production of pro-inflammatory cytokines by suppressing the activation of NF-κB signaling pathway in mouse peritoneal macrophages. Munronoid I reduced the LPS-, tumor necrosis factor alpha (TNF-α)- or interleukin 1 beta (IL-1ß)-induced transforming growth factor beta-activated kinase 1 (TAK1) phosphorylation and protein expression. Furthermore, the Munronoid I also promoted K48-linked ubiquitination and proteasomal degradation of TAK1. Taken together, these results demonstrated that Munronoid I exhibited anti-inflammatory activities both in vitro and in vivo, which might be a potential therapeutic candidate for the treatment of ALI and pulmonary inflammation.

USP14 negatively regulates RIG-I-mediated IL-6 and TNF-α production by inhibiting NF-κB activation.

Ubiquitin specific protease 14 (USP14) is a regulator of protein deubiquitination and proteasome activation, and has been implicated in negative regulation of type I IFN signaling pathway. However, the effect of USP14 on RNA virus-related inflammatory response has not been studied. Retinoic acid-inducible gene I (RIG-I) is the important pattern recognition receptor of the innate immunity to detect RNA viruses or intracellular Poly(I:C)-LMW. Here, we reported that USP14 knockdown increased pro-inflammatory cytokines production in macrophages upon VSV infection or intracellular Poly(I:C)-LMW stimulation. USP14-overexpressed HeLa cells exhibited a decrease in RIG-I-mediated IL-6 and TNF-α expression. IU1, USP14 inhibitor, significantly promotes pro-inflammatory cytokines production in VSV-infected mice in vivo. Furthermore, USP14 was also found to inhibit the RIG-I-triggered NF-κB activation by deubiquitinating K63-linked RIG-I. Thus, our results demonstrate that USP14 is a negative regulator of RIG-I-mediated inflammatory response.

Whole genome analysis reveals new insights into the molecular characteristics of Clostridioides difficile NAP1/BI/027/ST1 clinical isolates in the People's Republic of China.

Background: The epidemic new strain NAP1/BI/027/ST-1 of Clostridioides difficile (C. difficile) causes more severe coliti and a higher mortality rate than historical strains. However, C. difficile NAP1/BI/027/ST-1 (C. difficile RT027) infections have been rarely reported in Asia, particularly in China. Purpose: The objective of this study was to strengthen the understanding of the molecular characterizations of C. difficile RT027 in China. Patients and methods: Two C. difficile NAP1/BI/027/ST-1 were detected from two patients, and no additional isolates were found. Whole genome sequencing (WGS) was used to characterize two C. difficile RT027 isolates and control strain CD6 (from Hong Kong), and comparative genomic analysis was performed to compare genomic differences between seven isolates from Mainland China, CD6, and 10 isolates from North America and Europe. Results: The comparative genomic analysis revealed that isolates obtained from Mainlan China were outside of the two epidemic lineages, FQR1 and FQR2, and might have decreased virulence and transmissibility for outbreak. Furthermore, unique SNP mutations were detected in isolates obtained from Mainland China, which may affect the biological function of C. difficile. Conclusion: We speculate that C. difficile RT027 isolates in Mainland China may have different features, compared to those in North America and Europe.

Longitudinal investigation of carriage rates and genotypes of toxigenic Clostridium difficile in hepatic cirrhosis patients.

Toxigenic Clostridium difficile (C. difficile) carriers represent an important source in the transmission of C. difficile infection (CDI) during hospitalisation, but its prevalence and mode in patients with hepatic cirrhosis are not well established. We investigated longitudinal changes in carriage rates and strain types of toxigenic C. difficile from admission to discharge among hepatic cirrhosis patients. Toxigenic C. difficile was detected in 104 (19.8%) of 526 hepatic cirrhosis patients on admission, and the carriage status changed in a portion of patients during hospitalisation. Approximately 56% (58/104) of patients lost the colonisation during their hospital stay. Among the remaining 48 patients who remained positive for toxigenic C. difficile, the numbers of patients who were positive at one, two, three and four isolations were 10 (55.6%), three (16.7%), two (11.1%) and three (16.7%), respectively. Twenty-eight patients retained a particular monophyletic strain at multiple isolations. The genotype most frequently identified was the same as that frequently identified in symptomatic CDI patients. A total of 25% (26/104) of patients were diagnosed with CDI during their hospital stay. Conclusions: Colonisation with toxigenic C. difficile strains occurs frequently in cirrhosis patients and is a risk factor for CDI.

Protective Effect of Pediococcus pentosaceus LI05 Against Clostridium difficile Infection in a Mouse Model.

Clostridium difficile infection (CDI) is a major cause of infectious diarrhea among hospitalized patients. Probiotics could be instrumental in restoring the intestinal dysbiosis caused by CDI. Here, we examined the protective effect of Pediococcus pentosaceus LI05 in a mouse CDI model. C57BL/6 mice were administrated P. pentosaceus LI05 (LI05 group) or sterile anaerobic PBS (CDI group) everyday for 14 days. Mice were exposed to antibiotics cocktail for 5 days; then challenged with C. difficile strain VPI10463. Mice were monitored daily for survival and weight loss. Colonic tissue and serum samples were assessed for intestinal histopathology, intestinal barrier function and systemic inflammation. The oral administration of P. pentosaceus LI05 improved the survival rate and alleviated the histopathological impact of C. difficile. Compared to the CDI group, the levels of inflammatory mediators in the colon as well as inflammatory cytokines and chemokines in serum were substantially attenuated in the LI05 group. P. pentosaceus LI05 alleviated the CDI-induced of disruption of ZO-1, occludin and claudin-1. Additionally, fecal microbiome analysis showed an enrichment in the abundance of the Porphyromonadaceae and Rikenellaceae, while, the relative abundance of Enterobacteriaceae were decreased. Our results demonstrated that the preventive effect of P. pentosaceus LI05 against CDI was mediated via improving tight junction proteins and down-regulating the inflammatory response. Therefore, P. pentosaceus LI05 could be a promising probiotic in CDI.

Hospital-acquired Clostridium difficile infection in Mainland China: A seven-year (2009-2016) retrospective study in a large university hospital.

Clostridium difficile infection (CDI) is associated with risk for severe disease and high mortality. Little is known about the extent of hospital-acquired CDI in Mainland China. In this study, we aimed to investigate the annual CDI incidence, bacterial genotypes, risk factors for severe CDI and survival over a 7-year period. A total of 307 hospital-acquired CDI patients were enrolled, and 70.7% of these cases were male. CDI incidence was 3.4 per 10,000 admissions. Thirty-three different sequence types (STs) were identified, among which ST-54 (18.2%), ST-35 (16.6%) and ST-37 (12.1%) were the most prevalent. During the follow-up period, 66 (21.5%) patients developed severe CDI and 32 (10.4%) patients died in 30 days. Multivariate analysis revealed that bloodstream infection, pulmonary infection and C-reactive protein were significantly associated with severe CDI. After adjustment for potential confounders, old age, bloodstream infection, fever, mechanical ventilation, connective tissue disease, macrolide use and hypoalbuminaemia were independently associated with 30-day mortality in patients with CDI. The CDI prevalence has been low and stable in our center, and STs of Clostridium difficile were different from dominant STs in Western countries. Our data emphasize the need of continued education and surveillance of CDI to reduce the CDI burden in China.