Mechanism of isorhynchophylline in lipopolysaccharide-induced acute lung injury based on proteomic technology.

Isorhynchophylline (IRN), a tetracyclic indole alkaloid, has anti-inflammatory and antioxidant activities against cardiovascular diseases and central nervous system disorders. Acute lung injury (ALI) is a manifestation of inflammation concentrated in the lungs and has a high incidence rate and mortality The purpose of this study is to explain the mechanism of IRN in the treatment of acute lung injury and to provide a new scheme for clinical treatment. The experimental mice were divided into three groups: CTRL, LPS, LPS+IRN. The mouse model of ALI was established by inhaling LPS solution through nose. After continuous administration of IRN solution for 7 days, the mice in LPS+IRN group were killed and the lung tissue was collected for detection. Proteomic (Data are available via ProteomeXchange with identifier PXD050432) results showed that 5727 proteins were detected in mouse lung tissues, and 16 proteins were screened out. IRN could reverse the trend of these differential proteins. In addition, IRN can act on integrin αM to reduce neutrophil recruitment and thereby produce anti-inflammatory effects and may suppress neutrophil migration through the leukocyte transendothelial migration pathway. TUNEL and RT-PCR experiments revealed that LPS-induced ALI in mice increases the apoptosis of lung tissues, damage to alveolar epithelial cells and levels of inflammatory factors. Treatment with IRN can repair tissues, improve lung tissue pathology and reduce lung inflammation.

Mucosa color and size may indicate malignant transformation of chicken skin mucosa-positive colorectal neoplastic polyps.

BACKGROUND: Lipid metabolism reprogramming is suspected to exist in pre-cancerous lesions, including colorectal adenoma. Screening colonoscopy frequently reveals chicken skin mucosa (CSM; white or yellow-white speckled mucosa) surrounding colorectal polyps, caused by macrophages engulfing and accumulating the lipids decomposed by colon cells or adjacent tumors. CSM-positive colorectal polyps are associated with various diseases; however, their prognosis varies greatly. Cold snare polypectomy is commonly used to resect lesions up to 10 to 15 mm in diameter without signs of submucosal invasion but is controversial for CSM-positive colorectal polyps. Improved imaging is required to diagnose and treat CSM-positive colorectal polyps. AIM: To highlight the clinical significance of CSM surrounding colorectal polyps and clarify the associated treatment for endoscopists. METHODS: This retrospective cohort study included 177 patients with CSM-positive colorectal polyps diagnosed using endoscopy. All patient-related information was extracted from the Goldisc soft-clinic DICOM system or electronic medical record system. Based on the pathological results, patients were classified as non-neoplastic polyps (five juvenile polyps), neoplastic polyps, non-invasive high-grade neoplasia (NHGN), or submucosal invasive carcinoma (SM stage cancer). We analyzed and compared the clinical features, suspected risk factors for malignant transformation of neoplastic polyps, and early infiltration of submucosal carcinoma. RESULTS: The diameters of NHGN and SM polyps were much smaller than those of neoplastic polyps. Most NHGN polyps had a deeper red mucosal color. On logistic regression analyses, diameter and deeper red mucosal color were independent risk factors for malignant transformation of neoplastic polyps. Type 1 CSM was more common in high-grade intraepithelial neoplasia and SM; type 2 CSM was more common in neoplastic polyps. Logistic regression analyses revealed no significant differences in the malignant transformation of neoplastic polyps or early submucosal invasion of CSM-positive colorectal cancer. Changes in the CSM mucosa surrounding neoplastic polyps and submucosal invasion of colorectal cancer disappeared within 12 months. No tumor recurrence was found during either partial or complete endoscopic resection of the CSM. CONCLUSION: CSM-positive colorectal polyps > 1 cm in diameter or with deeper red mucosa may be related to NHGN. Resection of CSM surrounding colorectal adenomas did not affect tumor recurrence.

Identification of Central Genes and Regulatory Pathways Associated with Hyperlipidemia in Rats.

Hyperlipidemia is an independent risk factor for cardiovascular and cerebrovascular diseases. The transcriptomic data and the gene regulatory networks of hyperlipidemia are largely unclear. We analyzed the changes in liver gene expression and the serum levels of biochemical indicators in rats with hyperlipidemia induced by high-fat diet (HFD). The body weight, liver weight, and the serum levels of TG, TC, HDL-C, LDL-C, ALT, and AST were significantly higher in the hyperlipidemic rats compared to the healthy controls (P < 0.05). In addition, HFD feeding decreased the antioxidant capacity of the liver tissues and significantly increased the arteriosclerosis index (AI) (P < 0.05). There were 584 differentially expressed genes (DEGs) in the hyperlipidemia model compared to the control, with |log2FC|≥ 1 and P-adjust ≤ 0.05 as the thresholds. GO analysis of the DEGs revealed significant enrichment of 382 biological processes (BP), 18 cellular components (CC), and 40 molecular functions (MF). In addition, pathways related to bile secretion, cholesterol metabolism, and steroid hormone biosynthesis were significantly associated with hyperlipidemia. The key genes potentially involved in the blood lipid changes were Agt, Src, Gnai3, Cyp2c7, Cyp2c11, Cyp2c22, Apoa1, Apoe, and Srebf1. The genes and pathways identified in this study are potential intervention targets for hyperlipidemia and warrant further investigation.

Identification and quantification of nanoplastics (20-1000 nm) in a drinking water treatment plant using AFM-IR and Pyr-GC/MS.

Nanoplastics, owing to their small particle size, pose a significant threat to creatures, deserving heightened attention. Numerous studies have investigated microplastics pollution and their removal efficiency in drinking water treatment plants, none of which have involved nanoplastics due to lacking a suitable analytical method. This study introduced a feasible method of combing AFM-IR and Pyr-GC/MS to identify and quantify nanoplastics (20-1000 nm) for a preliminary understanding of their fate during drinking water treatment processes. Resolving of chemical functional groups and pyrolysis products from AFM-IR and Pyr-GC/MS data demonstrated the presence of PE and PVC nanoplastics in this drinking water treatment plant. The initial influent abundances of PE and PVC nanoplastics were 0.86 µg/L and 137.31 µg/L, with subsequent increase to 4.49 µg/L and 208.64 µg/L in ozonation contact tank unit. Then a gradual decreasing was observed along water process, achieving 98.4% removal of PE nanoplastics and 44.0% removal of PVC nanoplastics, respectively. Although this drinking water treatment plant has exhibited a certain level of nanoplastics removal efficiency, particular attention should be directed to the oxidation unit, which appears to be a significant source of nanoplastics. This study will lay a foundation for revealing nanoplastics pollution in the environment.

An epidemiological surveillance study (2021-2022): detection of a high diversity of Clostridioides difficile isolates in one tertiary hospital in Chongqing, Southwest China.

BACKGROUND: Clostridioides difficile is a bacterium that causes antibiotic-associated infectious diarrhea and pseudomembranous enterocolitis. The impact of C. difficile infection (CDI) in China has gained significant attention in recent years. However, little epidemiological data are available from Chongqing, a city located in Southwest China. This study aimed to investigate the epidemiological pattern of CDI and explore the drug resistance of C. difficile isolates in Chongqing. METHODS: A case-control study was conducted to investigate the clinical infection characteristics and susceptibility factors of C. difficile. The features of the C. difficile isolates were evaluated by testing for toxin genes and using multi-locus sequence typing (MLST). The susceptibility of strains to nine antibiotics was determined using agar dilution technique. RESULTS: Out of 2084 diarrhea patients, 90 were tested positive for the isolation of toxigenic C. difficile strains, resulting in a CDI prevalence rate of 4.32%. Tetracycline, cephalosporins, hepatobiliary disease, and gastrointestinal disorders were identified as independent risk factors for CDI incidence. The 90 strains were classified into 21 sequence types (ST), with ST3 being the most frequent (n = 25, 27.78%), followed by ST2 (n = 10, 11.11%) and ST37 (n = 9, 10%). Three different toxin types were identified: 69 (76.67%) were A+B+CDT-, 12 (13.33%) were A-B+CDT-, and 9 (10%) were A+B+CDT+. Although substantial resistance to erythromycin (73.33%), moxifloxacin (62.22%), and clindamycin (82.22%), none of the isolates exhibited resistance to vancomycin, tigecycline, or metronidazole. Furthermore, different toxin types displayed varying anti-microbial characteristics. CONCLUSIONS: The strains identified in Chongqing, Southwest China, exhibited high genetic diversity. Enhance full awareness of high-risk patients with HA-CDI infection, particularly those with gastrointestinal and hepatocellular diseases, and emphasize caution in the use of tetracycline and capecitabine. These findings suggest that a potential epidemic of CDI may occur in the future, emphasizing the need for timely monitoring.

Chicken skin mucosa surrounding small colorectal cancer could be an endoscopic predictive marker of submucosal invasion.

BACKGROUND: Chicken skin mucosa (CSM) surrounding colon polyps is a common endoscopic finding with pale yellow-speckled mucosa during a colonoscopy screening. Although reports about CSM surrounding small colorectal cancer are scarce, and its clinical significance in intramucosal and submucosal cancers is unclear, previous studies have suggested it could be an endoscopic predictive marker for colonic neoplastic and advanced polyps. Currently, because of the inaccurate preoperative evaluation by endoscopists, many small colorectal cancers, particularly lesions with a diameter < 2 cm, are improperly treated. Therefore, more effective methods are required to better assess the depth of the lesion before treatment. AIM: To explore potential markers of small colorectal cancer early invasion under white light endoscopy, providing patients with better treatment alternatives. METHODS: This retrospective cross-sectional study included 198 consecutive patients [233 early colorectal cancers (ECCs)] who underwent endoscopy or surgical procedures at the Digestive Endoscopy Center of Chengdu Second People's Hospital between January 2021 and August 2022. The participants had pathologically confirmed colorectal cancer with a lesion diameter < 2 cm and received endoscopic or surgical treatment, including endoscopic mucosal resection and submucosal dissection. Clinical pathology and endoscopy parameters, including tumor size, invasion depth, anatomical position, and morphology, were reviewed. Fisher's exact test, the χ2 test, and Student's t-test were used to analyze the patient's basic characteristics. Logistic regression analysis was used to examine the relationship between morphological characteristics, size, CSM prevalence, and ECC invasion depth under white light endoscopy. Statistical significance was set at P < 0.05. RESULTS: The submucosal carcinoma (SM stage) was larger than the mucosal carcinoma (M stage) with a significant difference (17.2 ± 4.1 vs 13.4 ± 4.6 mm, P < 0.01). M- and SM-stage cancers were common in the left colon; however, no significant differences were found between them (151/196, 77% and 32/37, 86.5%, respectively, P = 0.199). The endoscopic features of colorectal cancer revealed that CSM, depressed areas with clear boundaries, and erosion or ulcer bleeding were more common in the SM-stage cancer group than in the M-stage cancer group (59.5% vs 26.2%, 46% vs 8.7%, and 27.3% vs 4.1%, respectively, P < 0.05). CSM prevalence in this study was 31.3% (73/233). The positive rates of CSM in flat, protruded, and sessile lesions were 18% (11/61), 30.6% (30/98), and 43.2% (32/74), respectively, with significant differences (P = 0.007). CONCLUSION: CSM-related small colorectal cancer was primarily located in the left colon and could be a predictive marker of submucosal invasion in the left colon.

The porcine piRNA transcriptome response to Senecavirus a infection.

Introduction: Senecavirus A (SVA) belongs to the genus Senecavirus in the family Picornaviridae. PIWI-interacting RNAs (piRNAs) are a class of small Ribonucleic Acids (RNAs) that have been found in mammalian cells in recent years. However, the expression profile of piRNAs in the host during SVA infection and their roles are poorly understood. Methods: Here, we found the significant differential expression of 173 piRNAs in SVA-infected porcine kidney (PK-15) cells using RNA-seq and 10 significant differentially expressed (DE) piRNAs were further verified by qRT-PCR. Results: GO annotation analysis showed that metabolism, proliferation, and differentiation were significantly activated after SVA infection. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that significant DE piRNAs were mainly enriched in AMPK pathway, Rap1 pathway, circadian rhythm and VEGF pathway. It was suggested that piRNAs may regulated antiviral immunity, intracellular homeostasis, and tumor activities during SVA infection. In addition, we found that the expression levels of the major piRNA-generating genes BMAL1 and CRY1 were significantly downregulated after SVA infection. Discussion: This suggests that SVA may affect circadian rhythm and promote apoptosis by inhibiting the major piRNA-generating genes BMAL1 and CRY1. The piRNA transcriptome in PK-15 cells has never been reported before, and this study will further the understanding of the piRNA regulatory mechanisms underlying SVA infections.

Impact of Submucosal Saline Injection During Cold Snare Polypectomy for Colorectal Polyps Sized 3-9 mm: A Multicenter Randomized Controlled Trial.

INTRODUCTION: The role of submucosal injection during cold snare polypectomy (CSP) remains uncertain. In this study, we investigated the impact of submucosal saline injection during CSP for colorectal polyps sized 3-9 mm. METHODS: This was a multicenter randomized controlled trial conducted in 6 Chinese centers between July and September 2020 (ChiCTR2000034423). Patients with nonpedunculated colorectal polyps sized 3-9 mm were randomized in a 1:1 ratio to either CSP with submucosal injection (SI-CSP) or conventional CSP (C-CSP). The primary outcome was the incomplete resection rate (IRR). Secondary outcomes included procedure time, intraprocedural bleeding, delayed bleeding, and perforation. RESULTS: One hundred fifty patients with 234 polyps in the SI-CSP group and 150 patients with 216 polyps in the C-CSP group were included in the analysis. The IRR was not decreased in the SI-CSP group compared with that in the C-CSP group (1.7% vs 1.4%, P = 1.000). The median procedure time in the SI-CSP group was significantly longer than that in the C-CSP group (108 seconds vs 48 seconds, P < 0.001). The incidences of intraprocedural bleeding and delayed bleeding were not significantly different between the 2 groups ( P = 0.531 and P = 0.250, respectively). There was no perforation in either group. DISCUSSION: Submucosal saline injection during CSP for colorectal polyps sized 3-9 mm did not decrease the IRR or reduce adverse events but prolonged the procedure time.

Toxicity of polystyrene nanoplastics to human embryonic kidney cells and human normal liver cells: Effect of particle size and Pb2+ enrichment.

Nanoplastics pollution in drinking water has aroused wide concern, but their effects on human health are still poorly understood. Herein we explore the responses of human embryonic kidney 293T cells and human normal liver LO2 cells to polystyrene nanoplastics, mainly focusing on the effects of particle sizes and enrichment of Pb2+. When the exposed particle size is higher than 100 nm, there is no obvious death for these two different cell lines. As the particle size decreases from 100 nm, cell mortality goes up. Although the internalization of polystyrene nanoplastics in LO2 cells is at least 5 times higher than that in 293T cells, the mortality of LO2 cells is lower than that of 293T cells, illustrating that LO2 cells are more resistant to polystyrene nanoplastics than 293T cells. Additionally, the Pb2+ enrichment on polystyrene nanoplastics in water can further enhance their toxicity, which should be taken seriously. The cytotoxicity of polystyrene nanoplastics to cell lines works through a molecular mechanism involving oxidative stress-induced damage of mitochondria and cell membranes, resulting in a decrease in ATP production and an increase in membrane permeability. Referenced to nanoplastics pollution in drinking water, there is no necessary to panic about the adverse effects of plastic itself on human health, but the enrichment of contaminants should get more attention. This work provides a reference for the risk assessment of nanoplastics in drinking water to human health.

Enhanced ozonation of polystyrene nanoplastics in water with CeOx@MnOx catalyst.

The nanoplastics released into the environment pose a critical threat to creatures, and thus it is necessary to remove them. However, their natural decomposition usually takes years or even decades, which raises an imminent demand for an efficient removal technology. Herein we report a core-shell CeOx@MnOx catalyst for enhancing ozonation of polystyrene nanoplastics in water. Ozonation achieves 31.67% molecular weight removal of polystyrene nanoplastics in the first 10 min reaction, which is increased to 51.67% in catalytic ozonation by MnOx and further improved to 73.33% in catalytic ozonation via CeOx@MnOx. The remarkable thing is the CeOx@MnOx could achieve almost 96.70% molecular weight removal after 50 min reaction. The specific catalytic mechanism is ozone decomposes into reactive oxygen radicals (•OH, •O2- and 1O2) after capturing electrons from MnOx, improving the polystyrene nanoplastics removal. Meanwhile, the Mn averaged valence state increases, making it harder to donate electrons to ozone. This can be alleviated by encapsulating the CeOx core in the MnOx, enabling electrons replenishment from the CeOx core to the MnOx shell, which is verified by the experiment and density functional theory calculations. The repeated experiment demonstrates the CeOx@MnOx possesses excellent stability, maintaining 95.25-96.70% removal efficiency of polystyrene nanoplastics. This research provides a possibility for the efficient removal of nanoplastics in water.

Effect of laparoscopic surgery for colorectal cancer with N. O. S. E. on recovery and prognosis of patients.

OBJECTIVE: To investigate the effect of laparoscopic surgery in colorectal cancer (CRC) patients with natural orifice specimen extraction (NOSE) on the recovery and quality of life (QOL) of patients. MATERIAL AND METHODS: Ninety-two eligible patients were randomly assigned into two groups: the traditional laparoscopy group (L group, n = 46) and the laparoscopic transanal specimen extraction group (NL group, n = 46). General data, surgery-related indicators, postoperative recovery, and prognosis were compared and analyzed between the two groups. RESULTS: A total of 46 patients in each group were enrolled in this study. The general data and surgery-related indicators were comparable between the two groups (all p > .05). There were no significant differences in the time of first flatus, bleeding, obstruction, constipation, and infectious complications between the two groups (all p > .05). The differences in the incidence of postoperative diarrhea, pain degree, and satisfaction on the aesthetics of the abdominal wall showed significant differences (χ2 = 6.133, p = .013; χ2 = 12.116, p = .017; χ2 = 13.463, p = .004). The postoperative follow-up time was 3-53 months. There were no significant differences in the postoperative hospital stay, medical costs, hospital readmission rate, incidence of incisional hernia, overall survival, disease-free survival, and QOL between the two groups (all p > .05). Conclusion: Laparoscopic surgery with NOSE for eligible patients with CRC was a feasible choice.

Evaluation of Modified Rapid Carbapenem Inactivation Method (mrCIM) Combined with Rapid EDTA-Modified Carbapenem Inactivation Method (reCIM) to Detect Carbapenemase and Distinguish Metallo-Carbapenemase in Enterobacteriaceae Within Four Hours.

PURPOSE: To develop a rapid EDTA-modified carbapenem inactivation method (reCIM) combined with modified rapid carbapenem inactivation method (mrCIM) to detect carbapenemase and distinguish metallo-ß-lactamases from carbapenemases in Enterobacteriaceae in 4 hrs. MATERIALS AND METHODS: The sensitivities and specificities of mrCIM and reCIM were retrospectively evaluated in 247 carbapenem-resistant Enterobacteriaceae of which 107 were carbapenemase producers confirmed by PCR and sequencing. In addition, mrCIM and reCIM were prospectively evaluated with 47 carbapenem-resistant enterobacterial isolates. RESULTS: The sensitivity and specificity of mrCIM were 96.3% and 97.1% at 2.5 hrs post incubation, and the specificity increased to 98.6% at 3 hrs. The combined mrCIM and reCIM showed a sensitivity of 95.4% and a specificity of 100% at 2.5 hrs post incubation in identifying metallo-ß-lactamases, and the sensitivity increased to 97.0% at 3 hrs. These performance characteristics are comparable to mCIM and eCIM; however, compared with mCIM and reCIM tests which need at least 24 hrs to detect results, the mrCIM and reCIM required less than 4 hrs of total work time. CONCLUSION: The combined mrCIM and reCIM can be used to accurately and quickly detect carbapenemase and metallo-ß-lactamases in Enterobacteriaceae in 4 hrs and are suitable for routine use in most clinical microbiology laboratories.

Synthesis and biological evaluation of a new series of 1-aryl-3-[4-(pyridin-2-ylmethoxy)phenyl]urea derivatives as new anticancer agents.

The diaryl ureas are very important fragments in medicinal chemistry. By means of computer-aided design, 1-aryl-3-[4-(pyridin-2-ylmethoxy)phenyl]urea derivatives were designed and synthesized, and evaluated for their antiproliferative activity against A549, HCT-116, PC-3 cancer cell lines, and HL7702 human normal liver cell lines in vitro by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide colorimetric assay. Most of the target compounds demonstrate significant antiproliferative effects on all the selective cancer cell lines. The calculated IC50 values were reported. The target compound 1-(4-chlorophenyl)-3-{4-{[3-methyl-4-(2,2,2-trifluoroethoxy)pyridin-2-yl]methoxy}phenyl}urea (7u) demonstrated the most potent inhibitory activity (IC50 = 2.39 ± 0.10 µM for A549 and IC50 = 3.90 ± 0.33 µM for HCT-116), comparable to the positive-control sorafenib (IC50 = 2.12 ± 0.18 µM for A549 and IC50 = 2.25 ± 0.71 µM for HCT-116). Conclusively, 1-aryl-3-[4-(pyridin-2-ylmethoxy)phenyl]urea derivatives as the new anticancer agents were discovered, and could be used as the potential BRAF inhibitors for further research.

Characteristics of Clostridium difficile isolates and the burden of hospital-acquired Clostridium difficile infection in a tertiary teaching hospital in Chongqing, Southwest China.

BACKGROUND: Clostridium difficile infection (CDI), especially hospital-acquired Clostridium difficile infection (HA-CDI), continues to be a public health problem and has aroused great concern worldwide for years. This study aimed to elucidate the clinical and epidemiological features of HA-CDI and the characteristics of C.difficile isolates in Chongqing, Southwest China. METHODS: A case-control study was performed to identify the clinical incidence and risk factors of HA-CDI. C. difficile isolates were characterised by polymerase chain reaction (PCR) ribotyping, multilocus sequence typing (MLST), toxin gene detection and antimicrobial susceptibility testing. RESULTS: Of the 175 suspicious patients, a total of 122 patients with antibiotic-associated diarrhea (AAD) were included in the study; among them, 38 had HA-CDI. The incidence of AAD and HA-CDI was 0.58 and 0.18 per 1000 patient admissions, respectively. Chronic renal disease and cephalosporin use were independent risk factors for HA-CDI. Fifty-five strains were assigned into 16 sequence types (STs) and 15 ribotypes (RTs). ST2/RT449 (8, 14.5%) was the predominant genotype. Of the 38 toxigenic isolates, A + B + CDT- isolates accounted for most (34, 89.5%) and 1 A + B + CDT+ isolate emerged. No isolate was resistant to vancomycin, metronidazole or tigecycline, with A-B-CDT- being more resistant than A + B + CDT-. CONCLUSIONS: Different genotypes of C. difficile strains were witnessed in Chongqing, which hinted at the necessary surveillance of HA-CDI. Adequate awareness of patients at high risk of HA-CDI acquisition is advocated and cautious adoption of cephalosporins should be highlighted.

Design, Synthesis and Biological Evaluation of a New Series of 1-Aryl-3-{4-[(pyridin-2-ylmethyl)thio]phenyl}urea Derivatives as Antiproliferative Agents.

To discover new antiproliferative agents with high efficacy and selectivity, a new series of 1-aryl-3-{4-[(pyridin-2-ylmethyl)thio]phenyl}urea derivatives (7a-7t) were designed, synthesized and evaluated for their antiproliferative activity against A549, HCT-116 and PC-3 cancer cell lines in vitro. Most of the target compounds demonstrated significant antiproliferative effects on all the selective cancer cell lines. Among them, the target compound, 1-[4-chloro-3-(trifluoromethyl)phenyl]-3-{4-{{[3-methyl-4-(2,2,2-trifluoroethoxy)pyridin-2-yl]methyl}thio}phenyl}urea (7i) was identified to be the most active one against three cell lines, which was more potent than the positive control with an IC50 value of 1.53 ± 0.46, 1.11 ± 0.34 and 1.98 ± 1.27 µM, respectively. Further cellular mechanism studies confirmed that compound 7i could induce the apoptosis of A549 cells in a concentration-dependent manner and elucidated compound 7i arrests cell cycle at G1 phase by flow cytometry analysis. Herein, the studies suggested that the 1-aryl-3-{4-[(pyridin-2-ylmethyl)thio]phenyl}urea skeleton might be regarded as new chemotypes for designing effective antiproliferative agents.

Epidemiology, antifungal susceptibilities, and risk factors for invasive candidiasis from 2011 to 2013 in a teaching hospital in southwest China.

BACKGROUND: Invasive candidiasis (IC) is the most common cause of invasive fungal infections. Identification of risk factors for such infection may help in the empirical therapeutic decision-making process. We conducted this study to characterize the clinical epidemiology of such infection and to differentiate risk factors between Candida albicans and Candida non-albicans species. METHODS: We retrospectively evaluated patients with IC from 2011 to 2013. Clinical data, antibiotic therapy, underlying condition, and invasive procedures were analyzed and compared between C. albicans and C. non-albicans species. RESULTS: C. albicans was the most frequently isolated Candida species (48.6% of all IC patients), although C. non-albicans spp. were more commonly isolated overall. C. albicans, Candida tropicalis, and Candida parapsilosis have a high susceptibility rate to all antifungal agents (>90%), whereas Candida glabrata showed decreased susceptibility to fluconazole and itraconazole. Amphotericin B demonstrated excellent antifungal activity against all Candida species. Univariate analyses showed that IC patients with C. albicans had a higher ratio of older age (p = 0.008), solid tumor (p = 0.029), and hypoproteinemia (p = 0.019), whereas those with C. non-albicans spp. had a higher ratio of hospital length of stay (p = 0.005), usage of corticosteroids (p = 0.011), duration on corticosteroids (p = 0.005), chemotherapy (p = 0.022), hematologic malignancy (p = 0.039), neutropenia (p = 0.030), and usage of glycopeptides (p = 0.002). Multivariate analyses showed that a significant predictor of IC due to C. albicans was hypoproteinemia [odds ratio (95% confidence interval) = 2.133 (1.164-3.908), p = 0.014]. CONCLUSION: C. albicans was the most frequently isolated Candida species. The risk factors between C. albicans and C. non-albicans species are different.

Characterization of carbapenemases, extended spectrum ß-lactamases, quinolone resistance and aminoglycoside resistance determinants in carbapenem-non-susceptible Escherichia coli from a teaching hospital in Chongqing, Southwest China.

Carbapenem-resistant Escherichiacoli isolates harboring carbapenemases or combining an extended-spectrum ß-lactamase (ESBL) enzyme with loss of porins present an increasingly urgent clinical danger. Combined resistance to aminoglycosides and fluoroquinolones in carbapeneme non-susceptible (CNS) isolates will inevitably create problems. In the current study, we characterized the carbapenemases and ESBLs, and the prevalence of quinolone resistance determinants and aminoglycoside resistance determinants in carbapenem-non-susceptible (CNS) E.coli isolates from a teaching hospital in Chongqing, Southwest China in 2012. Thirty non-duplicated CNS E.coli isolates were screened via antimicrobial susceptibility testing, and the drug resistance profiles of the 30 strains were analyzed. Carbapenemase genes blaKPC-2, ESBL genes including blaCTX-M-3, blaCTX-M-14, blaCTX-M-55 and blaTEM, ARD genes including aac(6')-Ib, armA and rmtB, and QRD genes including qnrA, qnrB, qnrC, qnrD, qnrS and aac(6')-Ib-cr were identified and clonal relatedness was investigated by pulsed-field gel electrophoresis. Of the 30 isolates, 2 (6.7%) harbored carbapenemase gene blaKPC-2; 29 (96.7%) carried ESBLs; 20 (66.7%) were QRD positive; and 11 (36.7%) were ARD positive. Between the two blaKPC-2 positive strains, one contained ESBL, QRD and ARD genes, while the other expressed ESBL genes but was negative for both QRD and ARD genes. Of the 29 ESBLs positive isolates, 2 (6.9%) were carbapenemase positive, 19 (65.5%) were QRD positive, and 11 (37.9%) were ARD positive. PFGE revealed genetic diversity among the 30 isolates, indicating that the high prevalence of CNS E. coli isolates was not caused by clonal dissemination. Production of ESBLs was associated with the carbapenem resistance and QRD genes were highly prevalent among the CNS E. coli isolates. Multiple resistant genes were co-expressed in the same isolates. This is the first report of a multidrug resistant carbapenem-non-susceptible E.coli co-harboring resistant determinants blaKPC-2, blaCTX-M-14, blaCTX-M-55, blaTEM, aac(6')-Ib-cr, qnrB, aac(6')-Ib and rmtB from Chongqing, mainland China.

[Design, synthesis and evaluation of novel 2H-1, 4-benzodiazepine-2-ones as inhibitors of HIV-1 transcription].

HIV-1 trans-activator of transcription (Tat) plays a critical role in HIV-1 transcription. Based on the beta-turn motif present in HIV-1 Tat, a series of novel benzodiazepine analogs were designed as beta-turn mimetics and prepared from p-chloro-nitrobenzene/2-phenylacetonitrile, p-toluidine/benzoyl chloride, or (Z)-7-nitro-5-phenyl-1H-benzo[e][1, 4]diazepin-2(3H)-one (nitrazepam) through different synthetic routes. Preliminary biological evaluation indicated that compound 30 exhibited inhibitory activity on HIV-1 tat-mediated LTR transcription with EC50 of 25.0 micromol x L(-1) and showed no obvious cytotoxic effects on TZM-BI cells under the concentration of 100 micromol x L(-1).

1-(4-tert-Butyl-benz-yl)-2-(4-tert-butyl-phen-yl)-1H-benzimidazole.

In the mol-ecule of the title compound, C(28)H(32)N(2), the benzimidazole ring system is almost planar [maximum deviation = 0.0221 (15) Å] and forms dihedral angles of 85.86 (4) and 32.09 (6)° with the benzene rings. In the crystal structure, mol-ecules are linked into chains running parallel to the a axis by inter-molecular C-H⋯N hydrogen bonds. The methyl groups of a tert-butyl group are rotationally disordered over two positions with refined site-occupancy factors of 0.636 (4) and 0.364 (4).

(E)-4-[4-(Dimethyl-amino)benzyl-ideneamino]benzonitrile.

The mol-ecule of the title compound, C(16)H(15)N(3), displays a trans configuration with respect to the C=N double bond. The mol-ecule is not planar, the dihedral angle between the benzene rings being 57.83 (9)°. The crystal packing is stabilized only by van der Waals inter-actions.