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Objective Invasive candidiasis (IC), a life-threatening fungal infection prevalent among hospitalized patients, has highly variable regional epidemiology. We conducted a multicenter surveillance study to investigate recent trends in species distribution and antifungal susceptibility patterns among IC-associated Candida spp. in Beijing, China, from 2016 to 2017. Materials and Methods A total of 1496 non-duplicate Candida isolates, recovered from blood and other sterile body fluids of IC patients, were identified using matrix-assisted laser desorption/ionization time of flight mass spectrometry combined with ribosomal DNA internal transcribed spacer (ITS) region sequencing. Broth microdilution-based susceptibility testing using six antifungal agents was also conducted. Results Candida albicans was the most frequently isolated species (49.9%), followed by Candida tropicalis (15.5%), Candida glabrata (14.7%) and Candida parapsilosis (14.2%). No significant differences in species distribution were observed when compared with a 2012-2013 dataset. Overall, the rates of susceptibility to fluconazole and voriconazole were high among C. albicans (98% and 97.2%, respectively) and C. parapsilosis species complex (91.1% and 92%, respectively) isolates but low among C. tropicalis (81.5% and 81.1%, respectively) isolates. In addition, the rate of azole resistance among C. tropicalis isolates increased significantly (1.8-fold, P

Listeriosis, caused by Listeria monocytogenes, is a severe food-borne infection. The nationwide surveillance in China concerning listeriosis is urgently needed. In the present study, 144 L. monocytogenes isolates were collected from the samples of blood, cerebrospinal fluid (CSF), and fetal membrane/placenta in China for 12 years from 2008 to 2019. We summarized these listeriosis patients’ demographical and clinical features and outcomes. The susceptibility profile for 12 antibiotics was also determined by the broth microdilution method. Multilocus sequence typing (MLST) and serogroups of these listeria isolates were analyzed to designate epidemiological types. We enrolled 144 cases from 29 healthcare centers, including 96 maternal-neonatal infections, 33 cases of bacteremia, 13 cases of neurolisteriosis, and two cutaneous listeriosis. There were 31 (59.6%) fetal loss in 52 pregnant women and four (9.8%) neonatal death in 41 newborns. Among the 48 nonmaternal-neonatal cases, 12.5% (6/48) died, 41.7% (20/48) were female, and 64.6% (31/48) occurred in those with significant comorbidities. By MLST, the strains were distinguished into 23 individual sequence types (STs). The most prevalent ST was ST87 (49 isolates, 34.0%), followed by ST1 (18, 12.5%), ST8 (10, 6.9%), ST619 (9, 6.3%), ST7 (7, 4.9%) and ST3 (7, 4.9%). Furthermore, all L. monocytogenes isolates were uniformly susceptible to penicillin, ampicillin, and meropenem. In summary, our study highlights a high genotypic diversity of L. monocytogenes strains causing clinical listeriosis in China. Furthermore, a high prevalence of ST87 and ST1 in the listeriosis should be noted.

Objective The main objective of this study was to investigate the ameliorative effects of Palmatine (Pal) on Helicobacter pylori (H. pylori) induced chronic atrophic gastritis (CAG). Method Body function, serum biochemical indicators and histopathology were used to evaluate the pharmacodynamics of Pal on CAG rats. The target genes expression levels were verified and assessed by RT-PCR and immunohistochemistry (IHC). Moreover, UPLC-Q-TOF/MS analysis based on urine and serum was performed to identify the potential metabolites in the pathological process of CAG induced by H. pylori. Metabolic pathway analysis was performed to elucidate the metabolic network associated with Pal treatment of CAG. Results Pal (10, 20, 40 mg/kg/day) significantly restored the body function of CAG rats, reduced the serum biochemical indicators, and maintained the integrity of the gastric mucosal epithelial barrier while alleviated gastric histological damage. Metabolomics analysis shows that the therapeutic effect of Pal on CAG involves 10 metabolites and 10 metabolic pathways, of which the Taurine and hypotaurine metabolism, Glycerophospholipid metabolism and Pentose and glucuronate interconversions are closely related to the gastrointestinal protection of Pal, and these metabolic pathways crosstalk with each other due to the internet hub of citric acid cycle. Conclusions Metabolomics was used for the first time to identify potential biomarkers of CAG and to illuminate the therapeutic mechanism of Pal on CAG induced by H. pylori. The results provided a new insight for further research on CAG treatment.

Background: Zuojin Pill (ZJP), a famous Chinese medicinal formula, is widely accepted for treatment of chronic atrophic gastritis (CAG) in China. This study aimed to explore the therapeutic effects and mechanisms of ZJP in Helicobacter pylori (H. pylori) - induced chronic atrophic gastritis (CAG) in vivo and in vitro. Methods: CAG rat model was induced by H. pylori. ZJP (0.63, 1.26, and 2.52 g/kg, respectively) was administered orally for four weeks. Therapeutic effects of ZJP were identified by H&E staining and serum indices. In addition, cell viability, morphology and proliferation were detected by cell counting kit-8 (CCK8) and high-content screening assay (HCS), respectively. Moreover, relative mRNA expression and protein expression related to JMJD2B/COX-2/VEGF axis was detected to investigate the potential mechanisms of ZJP in CAG.Results: Results showed the symptoms (weight loss and gastric mucosa damage) of CAG were alleviated, and the contents of TNF-α in serum was markedly decreased after treating with ZJP. Moreover, cell viability, proliferation and morphology changes of GES-1 cells were ameliorated by ZJP intervention. In addition, proinflammatory genes and JMJD2B/COX-2/VEGF axis related genes were suppressed by ZJP administration in vitro and in vivo. Meanwhile, immunohistochemistry (IHC) and western blot confirmed down-regulation of these genes by ZJP intervention. Conclusion: ZJP treatment can alleviate gastric mucosal damage induced by H. pylori via JMJD2B/COX-2/VEGF axis.

Background: Zuojin Pill (ZJP), a famous Chinese medicinal formula, widely accepted for treatment of chronic atrophic gastritis (CAG) in China. This study aimed to explore the therapeutic effects and mechanisms of ZJP in Helicobacter pylori (H. pylori) - induced chronic atrophic gastritis (CAG) in vivo and in vitro. Methods: CAG rat model was induced by H. pylori. ZJP (0.63, 1.26, and 2.52 g/kg, respectively) was administered orally for four weeks. Therapeutic effects of ZJP were identified by H&E staining and serum indices. In addition, cell viability, morphology and proliferation were detected by cell counting kit-8 (CCK8) and high-content screening assay (HCS), respectively. Moreover, relative mRNA expression and protein expression related to JMJD2B/COX-2/VEGF axis was detected to investigate the potential mechanisms of ZJP in CAG. Results: Results showed the symptoms (weight loss and gastric mucosa damage) of CAG were alleviated, and the contents of TNF-α in serum was markedly decreased after treating with ZJP. Moreover, cell viability, proliferation and morphology changes of GES-1 cells were ameliorated by ZJP intervention. In addition, proinflammatory genes and JMJD2B/COX-2/VEGF axis related genes were suppressed by ZJP administration in vitro and in vivo. Meanwhile, immunohistochemistry (IHC) and western blot confirmed down-regulation of these genes by ZJP intervention. Conclusion: ZJP treatment can alleviate gastric mucosal damage induced by H. pylori via JMJD2B/COX-2/VEGF axis.

Objective Zuojin Pill (ZJP) containing two Chinese herbal drugs: Coptidis Rhizoma and Euodiae Fructus is a classical formula and is widely accepted as a treatment of chronic atrophic gastritis (CAG) in China. This study aimed to explore the therapeutic effect and mechanism of ZJP which attenuated H. pylori -induced CAG in vivo and in vitro.Methods: H. pylori (Helicobacter pylori) was used to induce CAG rat model. 0.63, 1.26, and 2.52 g/kg of ZJP (was administered orally for four weeks. Therapeutic effect of ZJP was identified by H & E staining and serum indices. In addition, cell viability, morphology and proliferation were detected by cell counting kit-8 and high-content screening assay. Gene and protein expression related to JMJD2B/COX-2/VEGF axis were detected to further investigate the potential mechanism.Results Compared with the control group, the ZJP groups showed a significant protection effects on Gastric mucosa, as indicated by the reduced loss of glands and inflammatory cell infiltration. Meanwhile, ZJP could ameliorate cell viability, morphology changes, and proliferation in GES-1 cells. Moreover, the ZJP treatment decreased the amount of IL-8, and TNF-α, indicating that it could reduce the level of inflammation, and decrease stomach damage. The expression of JMJD2B/COX-2/VEGF axis related genes and proteins were measured by real-time quantitative PCR, western blot and immunohistochemistry methods. The ZJP groups were found to decrease relative genes and protein expression level compared with the model group. ZJP could improve gastric mucosa protection and reduce inflammation level by inhibiting the expression level of JMJD2B/COX-2/VEGF axis.Conclusion Our data confirmed the effective therapy of ZJP in H. pylori -induced CAG, which supports the role of ZJP as an anti-inflammatory and protection of gastric mucosa agent in CAG induced by H. pylori . These results may provide helpful tools for the treatment of CAG.

Aims In this study, we will investigate the therapeutic effects of berberine (BBR) in Helicobacter pylori (H. pylori) induced chronic atrophic gastritis (CAG). Furthermore, potential mechanisms of BBR in regulating IRF8-IFN-γ signaling axis will also be investigated. Materials and methods H. pylori were utilized to establish CAG model of rats. Therapeutic effects of BBR on serum supernatant indices, and histopathology of stomach were analyzed in vivo. Moreover, GES-1 cells were infected by H. pylori, and intervened with BBR in vitro. Cell viability, morphology, proliferation, and quantitative analysis were detected by high-content screening (HCS) imaging assay. To further investigate the potential mechanisms of BBR, relative mRNA, immunohistochemistry and protein expression in IRF8-IFN-γ signaling axis were measured. Key findings Results showed serum supernatant indices including IL-17, CXCL1, and CXCL9 were downregulated by BBR intervention, while, G-17 increased significantly. Histological injuries of gastric mucosa induced by H. pylori also were alleviated. Moreover, cell viability and morphology changes of GES-1 cells were improved by BBR intervention. In addition, proinflammatory genes and IRF8-IFN-γ signaling axis related genes, including Ifit3, Upp1, USP18, Nlrc5, were suppressed by BBR administration in vitro and in vivo. The proteins expression related to IRF8-IFN-γ signaling axis, including Ifit3, IRF1 and Ifit1 were downregulated by BBR intervention.

Background Klebsiella pneumoniae exhibits prevalence in China. Little is known about the microbiological characterization of clinical K . pneumoniae isolates causing bloodstream infections (BSIs). Methods BSI-causing K . pneumoniae (BSIKpn) isolates were collected from five tertiary-care hospitals in Beijing, China. Their genetic relatedness was analyzed by pulsed-field gel electrophoresis (PFGE), antimicrobial susceptibility was determined by agar dilution method, and sequence type (ST) was evaluated by multilocus sequence typing (MLST). The hypermucoviscosity (HV) phenotype was identified by a positive string test. Carbapenemase, capsular serotypes and HV-associated genes were detected by PCR amplification. Results A total of 219 non-duplicated BSIKpn isolates were collected from Dec. 2013 to Dec. 2014 and categorized into 203 types (strains) which had a unique PFGE pattern. Among 203 BSIKpn strains, 105 different STs were identified. Overall, ST11 and ST23 were the predominant clones and detected from 14 strains (6.9%), respectively, followed by ST412 ( n = 13), ST37 ( n = 9), ST65 ( n = 7), ST15 ( n = 6), ST86 ( n = 6), ST592 ( n = 5) and ST29 ( n = 4). There were 74 STs containing only a single strain. Approximately 8.4% (17/203) of BSIKpn strains exhibited resistance to carbapenem and most of them produced K . pneumoniae carbapenemase (KPC). The majority (70.4%, 143/203) of BSIKpn isolates were associated with non-K1/K2/K5/K20/K54/K57 serotypes. Only 16.7% (34/203) of BSIKpn strains had K1/K2 serotypes. A total of 66 (32.5%) of the BSIKpn strains exhibited HV phenotype. The rmpA was a predominant factor in determining whether or not a BSIKpn strain had HV phenotype. Conclusions The majority of BSIKpn strains exhibited high level of genetic diversity and low resistance to commonly used antimicrobial agents. The specific capsular serotype and HV phenotype were not the major features of BSIKpn strains from China.

The spread of the plasmid-mediated colistin resistance gene, mcr-1 , into carbapenem-resistant Enterobacteriaceae (CRE) clinical isolates poses a significant threat to global health. Here we report the identification of three mcr-1 -harboring carbapenem-resistant Escherichia coli strains, collected from three patients in two provinces in China. Our results show that mcr-1 -harboring CRE strains have started to spread in different hospitals in China. In addition, this report presents the first description of chromosomal integration of mcr-1 into a carbapenem-resistant E. coli strain.

Shigella sonnei has become the dominant serotype causing shigellosis in Asian countries in recent years. In this study, we characterize the increasing trend of antibiotic resistance profiles and genotypes of S. sonnei isolates in the Beijing area. From January 2002 to December 2007, a total of 1108 Shigella isolates including 362 S. sonnei were recovered from diarrhea patients at the 302nd Hospital in Beijing. While the frequency of S. flexneri gradually decreased, S. sonnei gradually increased and became the dominant species. A total of 362 S. sonnei isolates were further analyzed for their antimicrobial profiles and 272 revived isolates were selected for genotyping analysis, respectively. High-level antimicrobial resistances were observed in sulfamethoxazole/trimethoprim (94.5%), ampicillin (40.3%), piperacillin (36.5%), and ceftriaxone (12.8%) with significant single- and multiple-drug resistance increase trends from 2002 to 2007 ( P = 0.0000). Pulsed-field gel electrophoresis analysis indicated that 263 (96.7%) S. sonnei belonged to 1 clonal genotype A, which were further divided into A1–A6 subtypes. While subtype A2 was dominant in the early stage of study years, subtype A4 started to emerge and increased significantly in later years. Antimicrobial resistance rates are statistically different among the 6 subtypes ( P = 0.0000), and A4 possessed the highest resistance rates to ampicillin (83.7%) and piperacillin (81.4%). Subtype A3 was highly clustered in inpatients compared to other subtypes ( P = 0.0145). This study indicates that a clonal S. sonnei strain has become dominant in the Beijing area, and subtype A4 is responsible for increased antibiotic resistance.

This is the first reported case of liver abscess attributable to Salmonella serovar Dublin infection and also the fourth case of Salmonella liver abscess complicated with hepatocellular carcinoma reported since 1990. Drainage combined with intravenous antibiotics resulted in improvement, but recovery regressed again. Subsequent hepatic left lobectomy led to full recovery.

Objective Periploca forrestii Schltr has been used as a Chinese folk medicine for the treatment of rheumatism, arthralgia and fractures. However, the anti-arthritic activity of Periploca forrestii saponin (PFS) and the active compound has still not been revealed. This study aimed to investigate the protective effects and mechanisms of PFS on collagen type II (CII) collagen-induced arthritis (CIA) mice. We sought to investigate whether PFS and Periplocin could regulate osteoclastogenesis, and if so, further investigation on its mechanism of action. Methods Arthritis was induced in female BALB/c mice by CIA method. PFS was administered at a dose of 50 mg/kg body weight once daily for five weeks. The effects of treatment in mice were assessed by histological and biochemical evaluation in sera and paws. Anti-osteoclastogenic action of PFS and Periplocin was identified using an osteoclast formation model induced by RANKL. Results PFS ameliorated paw erythema and swelling, inhibited bone erosion in ankle joint histopathological examination. PFS treatment resulted in decreased IgG2a, and increased IgG1 levels in the serum of CIA mice. Decreased TNF-α, and increased interleukin (IL)-4 and IL-22 levels were also found in PFS-treated mice. PFS inhibited the I-κBα phosphorylation, blocked nuclear factor (NF)-κB/p65 phosphorylation and abrogated AP-1/c-Fos activity. PFS downregulated toll-like receptor (TLR) 4, STAT3 and MMP-9 expression in CIA mice and RANKL-induced osteoclastogenesis. PFS and Periplocin inhibited RANKL-induced osteoclast formation in a dose dependent manner within nongrowth inhibitory concentration, and PFS decreased osteoclastogenesis-related marker expression, including cathepsin K and MMP-9. Conclusion This study revealed that the protective mechanism of PFS on CIA was associated with regulatory effects on proinflammatory factors and further on the crosstalk between NF-κB and c-Fos/AP-1 in vivo and in vitro. Therefore, PFS is a promising therapeutic alternative for the treatment of RA, evidencing the need to conduct further studies that can identify their active components in treating and preventing RA.