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Purpose: To analyze the differences in clinical distribution and antimicrobial resistance of pathogens among northern Anhui, central Anhui, and southern Anhui in 2021, and to provide a basis for the rational use of drugs for clinicians in different regions. Methods: Nonrepetitive pathogens isolated from clinical samples of inpatients and outpatients from 59 member units with qualified data in 2021 were obtained from the Anhui Province Antimicrobial Resistance Surveillance System, which was divided into northern Anhui, central Anhui, and southern Anhui by region. Identification and antimicrobial susceptibility analyses were carried out using the Vitek 2 Compact and standard disc diffusion method. The results were determined according to the American Clinical Laboratory Standards Institute in 2021 with data analyzed using WHONET 5.6 and SPSS 17.0. Results: A total of 133,268 pathogenic bacteria were isolated from clinical samples. Staphylococcus aureus (S. aureus) was the most common gram-positive bacterium and Escherichia coli (E. coli) was the most common gram-negative bacterium. Sputum was the main source of clinical specimens. The detection rates of methicillin-resistant S.aureus, methicillin-resistant coagulase-negative Staphylococcus, carbapenem-resistant E. coli, carbapenem-resistant Klebsiella pneumoniae (K. pneumoniae), carbapenem-resistant Acinetobacter baumannii, third-generation cephalosporin-resistant E. coli, and third-generation cephalosporin-resistant K. pneumoniae were higher in northern Anhui than in southern Anhui (P< 0.0001). E. coli, K. pneumoniae, and Pseudomonas aeruginosa were sensitive to amikacin. Strains resistant to vancomycin, linezolid, and teicoplanin were not isolated until 2021. Conclusion: There were significant differences in bacterial resistance in different regions of Anhui Province. Antibiotic resistance in northern Anhui was the most serious in 2021. Antimicrobial agents must be used according to the resistance of the bacteria in the local region. [ABSTRACT FROM AUTHOR]

The long-lasting infection of high-risk type (type 16 or type 18) human papillomavirus (HPV) is the main cause of gynecological and urinary malignancies. Given the high mortality rate after surgery, the development of a new molecular therapy would be of value to clinicians. The aim of the present study was to achieve targeted inactivation of the viral E6 gene in keratinocytes using the reprogrammed CRISPR-Cas13a system. To accomplish this, a reprogrammed CRISPR-Cas13a system, targeting both the HPV16/18 E6 genes was constructed using a guide RNA expressing vector. The expression levels of E6 protein were measured using western blot analysis after transfection of the vector into E6-transformed keratin oocytes. Cell proliferation was analyzed using CCK-8 assays and cell apoptosis was evaluated using Hoechst 33258 staining and ELISAs examining caspase-3 levels. The results indicated that both the HPV16/18 E6 genes can be inactivated using the CRISPR-Cas13a system. Furthermore, silencing E6 inhibited cell proliferation (14±1.8% on average) and induced apoptosis (80.2±3.2% on average) in E6-transformed keratinocytes but not in normal keratinocytes. In conclusion, results of the present study demonstrate that the reprogrammed CRISPR-Cas13a system has the potential for inactivating HPV E6 gene functions. [ABSTRACT FROM AUTHOR]

Methicillin-resistant Staphylococcus aureus (MRSA) is a major human pathogen that causes various diseases. Extensive researches highlight the significant role of gut microbiota and its metabolites, particularly spermidine, in infectious diseases. However, the immunomodulatory mechanisms of spermidine in MRSA-induced bloodstream infection remain unclear. Here, we confirmed the protective effects of spermidine in bloodstream infection in mice. Spermidine reduced the bacterial load and expression of inflammatory factors by shifting the macrophage phenotype to an anti-inflammatory phenotype, ultimately prolonging the survival of the infected mice. The protective effect against MRSA infection may rely on the elevated expression of protein tyrosine phosphatase nonreceptor 2 (PTPN2). Collectively, these findings confirm the immunoprotective effects of spermidine via binding to PTPN2 in MRSA bloodstream infection, providing new ideas for the treatment of related infectious diseases.

Klebsiella pneumoniae, a pathogen of critical clinical concern, urgently demands effective therapeutic options owing to its drug resistance. Polymyxins are increasingly regarded as a last-line therapeutic option for the treatment of multidrug-resistant (MDR) Gram-negative bacterial infections. However, polymyxin resistance in K. pneumoniae is an emerging issue. Here, we report that gallium nitrate (GaNt), an antimicrobial candidate, exhibits a potentiating effect on colistin against MDR K. pneumoniae clinical isolates. To further confirm this, we investigated the efficacy of combined GaNt and colistin in vitro using spot dilution and rapid time-kill assays and growth curve inhibition tests and in vivo using a murine lung infection model. The results showed that GaNt significantly increased the antimicrobial activity of colistin, especially in the iron-limiting media. Mechanistic studies demonstrated that bacterial antioxidant activity was repressed by GaNt, as revealed by RNA sequencing (RNA-seq), leading to intracellular accumulation of reactive oxygen species (ROS) in K. pneumoniae, which was enhanced in the presence of colistin. Therefore, oxidative stress induced by GaNt and colistin augments the colistin-mediated killing of wild-type cells, which can be abolished by dimethyl sulfoxide (DMSO), an effective ROS scavenger. Collectively, our study indicates that GaNt has a notable impact on the antimicrobial activity of colistin against K. pneumoniae, revealing the potential of GaNt as a novel colistin adjuvant to improve the treatment outcomes of bacterial infections. IMPORTANCE This study aimed to determine the antimicrobial activity of GaNt combined with colistin against Klebsiella pneumoniae in vitro and in vivo . Our results suggest that by combining GaNt with colistin, antioxidant activity was suppressed and reactive oxygen species accumulation was induced in bacterial cells, enhancing antimicrobial activity against K. pneumoniae. We found that GaNt functioned as an antibiotic adjuvant when combined with colistin by inhibiting the growth of multidrug-resistant K. pneumoniae. Our study provides insight into the use of an adjuvant to boost the antibiotic potential of colistin for treating infections caused by multidrug-resistant K. pneumoniae., Competing Interests: The authors declare no conflict of interest.

Recent research evidence documents that lncRNAs (long non-coding RNAs lncRNAs) play a pivotal role in the tumorigenesis and development of tumors. LncRNA SNGH3 (small nucleolar RNA host gene 3) is highly expressed in numerous forms of cancer, serving as an oncogene in cancer progression. Nonetheless, the clinical relationship, along with the mechanism of SNGH3 in bladder cancer, have not been studied. Herein, the findings exhibited upregulation of SNGH3 in bladder cancer tissues, along with the cell lines. Furthermore, overexpressed SNGH3 was positively linked to the TNM stage, as well as the histological grade of bladder cancer. Moreover, the silencing of SNGH3, using CRISPR-dCas9, suppressed cell growth along with migration, but elevated bladder cancer cell apoptosis. In summary, we established that SNGH3 serves as a bladder cancer oncogene and could be employed as a prospective diagnostic marker for clinical use, and is also a therapeutic target for CRISPR-mediated gene therapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Cao, Hu, Zhang, Li, Guo, Wei, Zhang, Wang and Li.)

CRISPR-CasRx technology provides a new and powerful method for studying cellular RNA in human cancer. Herein, the pattern of expression of long noncoding RNA 00341 (LINC00341) as well as its biological function in bladder cancer were studied using CRISPR-CasRx. qRT-PCR was employed to quantify the levels of expression of LINC00341 in tumor tissues along with the matched non-tumor tissues. sgRNA targeting LINC00341 or the sgRNA negative control were transiently transfected into the T24 as well as 5,637 human bladder cancer cell lines. CCK-8, ELISA as well as wound healing methods were employed to explore cell proliferation, apoptosis and migration, respectively. The tumorigenicity experiment in nude mice also performed to detect cell proliferation. The expression of p21, Bax as well as E-cadherin were assayed using western blot. The results demonstrated that LINC00341 was overexpressed in bladder cancer in contrast with the healthy tissues. The LINC00341 expression level in high-grade tumors was higher in contrast with that in low-grade tumors. The expression of linc00341 was higher relative to that of non-invasive tumors. In T24 as well as 5637-cell lines harboring LINC00341-sgRNA, inhibition of cell proliferation ( in vitro and in vivo ), elevated apoptosis rate and diminished migration ability. Moreover, silencing LINC00341 upregulated the expressions of p21, Bax as well as E-cadherin. Knockout of these genes could eliminate the phenotypic changes caused by sgRNA targeting LINC00341. Our data demonstrate that LINC00341 has a carcinogenic role in human bladder cancer., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Li, Cao, Zhang, Li, Wang, Zhou, Wei, Guo, Liu, Liu, Zhang and Liu.)

Insulin-like growth factor binding protein 4-1 (IGFBP4-1), a new long noncoding RNA (lncRNA), has been reported to contribute to tumorigenesis and has been suggested to be a poor prognostic marker in human lung cancer. However, there still lacks basic studies that investigated the biological role of IGFBP4-1 in bladder urothelial carcinoma to date. In this study, we investigated the relationship between IGFBP4-1 expression and prognosis in patients with bladder cancer. Cell proliferation, cell cycle and cell apoptosis assays were performed to assess IGFBP4-1 function by up-regulating or down-regulating IGFBP4-1 in bladder cancer cells. A xenograft mice model was used to validate the in vitro results. Blockade of Janus kinase-signal transducer and activator of transcription pathway (JAK/STAT) was used to evaluate JAK/STAT signaling activity. The results showed that IGFBP4-1 was overexpressed in bladder cancer tissues compared with that in normal bladder tissues, and its expression level was positively correlated with poor prognosis in bladder cancer patients. Overexpression of IGFBP4-1 markedly promoted cell proliferation and cell cycle progression, and inhibited cell apoptosis, while knockdown of IGFBP4-1 notably suppressed the proliferation, promoted cell apoptosis, and induced cell cycle arrest at the G0/G1 phase. Mechanistically, we revealed that IGFBP4-1 promotes the activation of the JAK/STAT pathway in bladder cancer cells. Moreover, the JAK/STAT inhibitor dramatically blocked the tumor-promoting activity of IGFBP4-1. Tumor growth in vivo was also suppressed by knocking down of IGFBP4-1. In conclusion, IGFBP4-1 promoted bladder cancer progression by activating the JAK/STAT signaling pathway. These findings suggest that IGFBP4-1 exhibits an oncogenic role in the development of human bladder cancer., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)