Epidemiological characteristics of New Delhi Metallo-ß-Lactamase-producing Enterobacteriaceae in the Fourth hospital of Hebei Medical University.

The epidemiological characteristics of New Delhi Metallo-ß-Lactamase-Producing (NDM) Enterobacteriaceae were analyzed to provide theoretical support for clarifying the distribution characteristics of carbapenem-resistant Enterobacteriaceae (CRE) in the hospital environment and early identification of susceptible patients. From January 2017 to December 2021,42 strains of NDM-producing Enterobacteriaceae were gathered from the Fourth Hospital of Hebei Medical University, primarily Escherichia coli, Klebsiella pneumoniae, and Enterobacter cloacae. The micro broth dilution method combined with the Kirby-Bauer method was used to determine the minimal inhibitory concentrations (MICs) of antibiotics. The carbapenem phenotype was detected by the modified carbapenem inactivation method (mCIM) and EDTA carbapenem inactivation method (eCIM). Carbapenem genotypes were detected by colloidal gold immunochromatography and real-time fluorescence PCR. The results of antimicrobial susceptibility testing showed that all NDM-producing Enterobacteriaceae were multiple antibiotic resistant, but the sensitivity rate to amikacin was high. Invasive surgery prior to culture, the use of excessive amounts of different antibiotics, the use of glucocorticoids, and ICU hospitalization were clinical characteristics of NDM-producing Enterobacteriaceae infection. Molecular typing of NDM-producing Escherichia coli and Klebsiella pneumoniae was carried out by Multilocus Sequence Typing (MLST), and the phylogenetic trees were constructed. Eight sequence types (STs) and two NDM variants were detected in 11 strains of Klebsiella pneumoniae, primarily ST17, and NDM-1. A total of 8 STs and 4 NDM variants were detected in 16 strains of Escherichia coli, mainly ST410, ST167, and NDM-5. For high-risk patients who have CRE infection, CRE screening should be done as soon as feasible to adopt prompt and efficient intervention measures to prevent outbreaks in the hospital.

Pyroptosis Provides New Strategies for the Treatment of Cancer.

Cancer is an important cause of death worldwide. The main types of cancer treatment are still surgery, chemotherapy and radiotherapy, and immunotherapy is becoming an important cancer treatment. Pyroptosis is a type of programmed cell death that accompanies an inflammatory response. This paper reviews the recent research progress in pyroptosis in tumors. Pyroptosis has been observed since 1986 and until recently has been recognized as programmed cell death mediated by GSDM family proteins. The molecular pathway of pyroptosis depends on the inflammasome-mediated caspase-1/GSDMD pathway, which is the canonical pathway, and the caspase-4/5/11/GSDMD pathway, which is the noncanonical pathway. Other pathways include caspase3/GSDME. Pyroptosis is a double-edged sword that is closely related to the tumor immune microenvironment. On the one hand, pyroptosis produces a chronic inflammatory environment, promotes the transition of normal cells to tumor cells, helps tumor cells achieve immune escape, and promotes tumor growth and metastasis. On the other hand, some tumor cell treatments can induce pyroptosis, which is a nonapoptotic form of cell death. Additionally, pyroptosis releases inflammatory molecules that promote lymphocyte recruitment and enhance the immune system's ability to kill tumor cells. With the advent of immunotherapy, pyroptosis has been shown to enhance the antitumor efficacy of immune checkpoint inhibitors. Some antineoplastic agents, such as chemotherapeutic agents, can also exert antineoplastic effects through the pyroptosis pathway. Pyroptosis, which is a programmed cell death mode, has been the focus of research in recent years, and the relationship between pyroptosis, tumors and tumor immunity has attracted attention, but there are still some questions to be answered regarding the specific mechanism. Further study of pyroptosis would aid in developing new antitumor therapies and has great clinical prospects.

Acupuncture for patients with chronic pruritus: protocol of a systematic review and meta-analysis.

INTRODUCTION: Chronic pruritus (CP) frequently occurs in many skin and systemic diseases, and adversely affects quality of life. This systematic review aims to evaluate treatment effects of acupuncture on CP. METHODS AND ANALYSIS: An electronic and manual search will be conducted for all acupuncture treatments for CP, from the inception date of predefined database up to 28 February 2020. Databases include PubMed, Embase, Springer, Web of Science, the Cochrane Library, the World Health Organization International Clinical Trial Registration Platform, the Chinese Medicine Database, the China National Knowledge Infrastructure, the Chinese Biomedical Literature Database, the China Science Journal Database and the Wanfang Database. Other sources, including existing systematic reviews, conference proceedings and reference lists of identified publications will also be searched. Additionally, any clinical randomised controlled trials related to acupuncture treatment for CP, regardless of the publication status and language limitations, will be included. Study selection, data extraction and research quality assessments will be conducted independently by two researchers. The primary outcome measures include the Visual Analogue Scale, Urdu 5D-Itch Scale or other validated scales implemented after at least 2 weeks of treatment. Secondary outcomes include the effective rate, Quality of Life Scale (eg, the EQ-5D third level, the Dermatology Life Quality Index, etc.), Pittsburgh Sleep Quality Index, recurrence rate during the follow-up period and adverse events. If possible, meta-analyses will be performed using RevMan V.5.3 statistical software; otherwise, a descriptive analysis or subgroup analysis will be conducted. The results will be presented as the risk ratio of the binary data and the mean difference (MD) or standardised MD of the continuous data. ETHICS AND DISSEMINATION: This systematic review protocol does not require formal ethical approval because the data are not personalised. It will be published in peer-reviewed journals and presented at international academic conferences. PROSPERO REGISTRATION NUMBER: CRD42019136727.

Higher neutrophil-lymphocyte ratio is associated with better prognosis of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide; its morbidity and mortality have both recently increased. Lately, the role played by the neutrophil-lymphocyte ratio (NLR) in the development of HCC has attracted attention. However, the exact relationship is not fully understood.A total of 538 participants diagnosed with HCC were recruited between 2010 and 2018. Their relevant routine blood parameters were measured, including NLR. Pearson Chi-Squared test, Spearman Rho test, and logistic regression analysis were performed to explore any correlations between NLR and HCC. A receiver operating characteristic (ROC) curve analysis was performed to determine the usefulness of NLR for predicting HCC. Univariate and multivariate Cox regression analysis for relevant routine blood parameters and any relationships with overall survival (OS) were performed. The Kaplan-Meier method was used to explore any further relationships with OS.NLR was significantly correlated with HCC tumor size by Pearson Chi-Squared test (P = .008). Furthermore, Spearman correlation coefficient showed that HCC tumor size was significantly correlated with NLR (P = .115, P = .008). NLR could sensitively and specifically predict HCC tumor size (area under the curve [AUC], 0.605; 95% confidence interval [CI], 0.429-0.743; P = .000). Higher NLR in patients with HCC was correlated with better OS (hazard ratio [HR] = 0.584; P = .000).A close correlation existed between increased NLR and HCC; NLR could sensitively and specifically predict HCC. High NLR might be an independent protective factor in the prognosis of patients with HCC.

Effect of Chinese medicine prescription on nephrotic syndrome: A protocol for systematic review and meta-analysis.

BACKGROUND: Nephrotic syndrome (NS) is a common chronic recurrent kidney disease. Many trials have shown that Chinese medicine prescription (CMP) can effectively treat NS. The program aims to evaluate the efficacy and safety of CMP for NS. METHODS: This systematic evaluation will entail an electronic and manual search of all CMP for NS from inception to February, 2020, regardless of the publication status or language. Databases include PubMed, Embase, Springer, Web of Science, the Cochrane Library, the World Health Organization International Clinical Trial Registration Platform, the Chinese Medicine Database, the China National Knowledge Infrastructure, the Chinese Biomedical Literature Database, the China Science Journal Database, and the Wanfang Database. Other sources of information, including bibliographies and meeting minutes for identified publications, will also be searched. A manual search for grey literature, including unpublished conference articles will be performed. Additionally, any clinical randomized controlled trials related to CMP for NS, regardless of the publication status and language limitations, will be included in the study. Study selection, data extraction, and research quality assessments will be conducted independently by 2 researchers. The main result was the total clinical efficacy rate or other validated scales after at least 2 weeks of treatment. Secondary outcomes included 24-hour urine protein quantification, blood urea nitrogen, serum creatinine, C-reactive protein, tumor necrosis factor-α, and interleukin 6, recurrence rates and adverse events during follow-up. Implement the Cochrane RevMan V5.3 bias assessment tool to assess bias risk, data integration risk, meta-analysis risk, and subgroup analysis risk (if conditions are met). Mean difference, standard mean deviation and binary data will be used to represent continuous results. RESULTS: This study will provide a comprehensive review and evaluation of CMP for the treatment of NS. CONCLUSION: This study will provide new evidence for evaluating the effectiveness and side effects of CMP on NS. Since the data is not personalized, formal ethical approval is not required. INPLASY REGISTRATION NUMBER: INPLASY202040181.

Effect of acupuncture on chronic bronchitis: A protocol for systematic review and meta-analysis.

INTRODUCTION: Chronic bronchitis (CB) is a clinically common and recurrent respiratory disease. However, many trials have shown that acupuncture can effectively treat CB. There is currently no systematic review of this therapy. The plan is to evaluate the effectiveness and safety of this treatment in patients with CB. METHODS AND ANALYSIS: This systematic evaluation will entail an electronic and manual search of all acupuncture for CB from inception to December 31, 2020, regardless of the publication status or language. Databases include PubMed, Embase, Springer, Web of Science, the Cochrane Library, the World Health Organization International Clinical Trial Registration Platform, the Chinese Medicine Database, the China National Knowledge Infrastructure, the Chinese Biomedical Literature Database, the China Science Journal Database, and the Wanfang Database. Other sources of information, including bibliographies and meeting minutes for identified publications, will also be searched. A manual search for grey literature, including unpublished conference articles will be performed. Additionally, any clinical randomized controlled trials related to acupuncture for CB, regardless of the publication status and language limitations, will be included in the study. Study selection, data extraction, and research quality assessments will be conducted independently by 2 researchers. The main result was the Change in cystic fibrosis transmembrane conductance regulator function as measured by sweat chloride analysis or treatment effect. Secondary outcomes included Quality of life (eg, SF-36), change in Breathlessness, Cough, and Sputum Scale score, follow-up relapse rate, and adverse events. The system searches for randomized controlled trials of this therapy for CB. Implement the Cochrane RevMan V5.3 bias assessment tool to assess bias risk, data integration risk, meta-analysis risk, and subgroup analysis risk (if conditions are met). Mean difference, standard mean deviation, and binary data will be used to represent continuous results. RESULTS: This study will provide a comprehensive review and evaluation of the available evidence for the treatment of CB using this therapy. CONCLUSION: This study will provide new evidence to evaluate the effectiveness and side effects of acupuncture on CB. Because the data are not personalized, no formal ethical approval is required. PROSPERO REGISTRATION NUMBER: CRD42020170287.

l-Theanine prevents ETEC-induced liver damage by reducing intrinsic apoptotic response and inhibiting ERK1/2 and JNK1/2 signaling pathways.

l-Theanine (LTA; γ-glutamylethylamide), a peculiar non-protein-derived amino acid isolated from tea, is widely used as a functional ingredient and dietary supplement. l-Theanine has been confirmed to have hepatoprotective effects, but the underlying mechanism remains unknown. This study investigated the protective effect of l-Theanine-in vivo, using an enterotoxigenic Escherichia coli (ETEC)-infected mouse model. l-Theanine significantly decreased the elevated serum activities of both aspartate aminotransferase (AST) and alanine aminotransferase (ALT), two biomarkers of hepatic impairment. This was consistent with histopathological images from the microscopic observation of liver tissue. In addition, l-theanine significantly increased the mRNA and protein expression of Bcl-2 and decreased the expression of Bax, anti- and pro-apoptotic molecules, respectively, compared with levels in the ETEC control group. The expression of cleaved caspase-3 protein in the group pre-treated with l-theanine was significantly lower than that in the ETEC group. Additionally, decreases in extracellular signal-regulated kinase (ERK1/2) and c-Jun NH2-terminal kinase(JNK1/2) MAPK phosphorylation were observed in the l-theanine pre-treated group. Our study demonstrates that l-theanine possesses anti-apoptotic activity, which can be attributed to suppression of the intrinsic mitochondria-mediated apoptosis and MAPK phosphorylation signaling pathways.

Stem cells derived from human first-trimester umbilical cord have the potential to differentiate into oocyte-like cells in vitro.

Compared to stem cells derived from human term umbilical cord, stem cells derived from human first-trimester umbilical cord (hFTUC) exhibit a significantly greater proliferative potential, and more efficiency in terms of their in vitro differentiation. In the present study, we investigated whether hFTUC-derived stem cells are able to differentiate into germ cells. The hFTUC-derived stem cells were first isolated, expanded and then cultured in differentiation medium containing human follicular fluid, follicle-stimulating hormone (FSH)/luteinizing hormone (LH) and estradiol for 24 days. During the period of induction, a subpopulation of the cultured cells appeared that had a morphological resemblance to primordial germ cells (PGCs) and cumulus-oocyte complex (COC)-like cells, and oocyte-like cells (OLCs). The PGC-like cells expressed specific markers indicative of germ cell formation such as octamer-binding transcription factor 4 (OCT4), stage-specific embryonic antigen 1 (SSEA1), B lymphocyte-induced maturation protein-1 (Blimp1), PR domain containing 14 (Prdm14), transcription factor AP-2 gamma (Tfap2C), VASA, STELLA, deleted in azoospermia-like (DAZL) and interferon-induced transmembrane protein 3 (IFITM3). The OLCs, which contained a single germinal vesicle, expressed oocyte-specific markers, such as synaptonemal complex protein 3 (SCP3), growth/differentiation factor-9 (GDF9), GDF9B and zona pellucida (ZP)1, ZP2 and ZP3. The COC-like cells secreted estradiol, vascular endothelial growth factor and leukemia inhibitory factor. Thus, our findings suggest that hFTUC-derived stem cells have an intrinsic ability to differentiate into OLCs, which may provide an in vitro model for the identification of factors involved in germ cell formation and differentiation.

[Psoralen induces rat mesenchymal stem cell differentiation towards male germ cells in vitro].

OBJECTIVE: To test the hypothesis that psoralen induces rat mesenchymal stem cells (RMSCs) to differentiate towards male germ cells. METHODS: RMSCs were induced by psoralen at the final concentration of 3.0 µg/ml, and the morphological changes of the cells were detected microscopically and the cell proliferation changes were measured by MTT assay. The expressions of 7 representative marker genes of male germ cells, namely Oct-4, Stra8, RVLG, SCP3, TNP2, Itgb1, and Itga6, were investigated in the induced cells by real-time quantitative PCR. RESULTS: RMSCs showed no obvious morphological changes after induction with 3.0 µg/ml psoralen for 72 h. Psoralen induction for 5 days did not significantly affect the proliferation of RMSCs; Psoralen induction for 72 h, however, significantly up-regulated the genes Oct-4, Stra8, SCP3, and Itgb1 (P<0.05) without affecting the expressions of the genes RVLG, TNP2, or Itga6 (P>0.05). CONCLUSION: Psoralen may participate in the differentiation of RMSCs towards male germ cells.

Bioavailability, metabolism and disposition of oral pazopanib in patients with advanced cancer.

1. Pazopanib (Votrient) is an oral tyrosine kinase inhibitor that was recently approved for the treatment of renal cell carcinoma and soft tissue sarcoma. 2. In this two-part study, we investigated the metabolism, disposition of [(14)C]pazopanib, and the oral bioavailability of pazopanib tablets in patients with advanced cancer. 3. In part A, three men each received a single oral dose of [(14)C]pazopanib in suspension (400 mg, 70 µCi). Pazopanib was the predominant drug-related component in circulation. Two metabolites derived from hydroxylation and one from N-demethylation were also circulating, but were minor, each accounting for <5% of plasma radioactivity. Faecal elimination predominated, accounting for 82.2% of the administered radio-dose, with negligible renal elimination (2.6% of dose). Pazopanib was primarily excreted as the unchanged drug in faeces (67% of dose). 4. In part B, seven additional patients received a single intravenous administration of 5 mg pazopanib (day 1) followed by oral administration of 800 mg pazopanib tablet once daily for 26 days (days 3 or 5-28). In the three evaluable patients from part B, pazopanib had a slow plasma clearance and a small volume of distribution. The absolute oral bioavailability of the 800 mg pazopanib tablet ranged from 14% to 39%.

Metabolism and disposition of eltrombopag, an oral, nonpeptide thrombopoietin receptor agonist, in healthy human subjects.

The metabolism and disposition of eltrombopag, the first-in-class small molecule human thrombopoietin receptor agonist, were studied in six healthy men after a single oral administration of a solution dose of [(14)C]eltrombopag (75 mg, 100 µCi). Eltrombopag was well tolerated. The drug was quickly absorbed and was the predominant circulating component in plasma (accounting for 63% of the total plasma radioactivity). A mono-oxygenation metabolite (M1) and acyl glucuronides (M2) of eltrombopag were minor circulating components. The predominant route of elimination of radioactivity was fecal (58.9%). Feces contained approximately 20% of dose as glutathione-related conjugates (M5, M6, and M7) and another 20% as unchanged eltrombopag. The glutathione conjugates were probably detoxification products of a p-imine methide intermediate formed by metabolism of M1, which arises through cytochrome P450-dependent processes. Low levels of covalently bound drug-related intermediates to plasma proteins, which could result from the reaction of the imine methide or acyl glucuronide conjugates with proteins, were detected. The bound material contributes to the longer plasma elimination half-life of radioactivity. Renal elimination of conjugates of hydrazine cleavage metabolites (mostly as M3 and M4) accounted for 31% of the radiodose, with no unchanged eltrombopag detected in urine.