Case report: A rare case of skin abscess caused by coinfection of Actinobaculum schaalii and Actinomyces turicensis.

Skin abscess is one of the most common infections of the skin and soft tissues. However, anaerobic bacteria are infrequently identified as the causative agents of this particular form of abscess. In this case, a 34-year-old pregnant woman was diagnosed with a skin abscess with the use of ultrasonography. The microbiological analysis results of the purulent fluid revealed the coinfection of Actinobaculum schaalii and Actinomyces turicensis. The patient was first treated empirically with 3 days of cefathiamidine, which resulted in no symptom improvement. Subsequently, a surgical procedure involving incision and draining was performed, with the administration of ceftriaxone. After 7 days of antibiotic intervention, the patient exhibited a satisfactory recovery. Clinicians need to be aware of other types of infections that might be attributed to Actinobaculum schaalii and Actinomyces turicensis, in addition to urinary tract infections.

A rare bacteremia caused by Fannyhessea vaginae in a pregnant woman: case report and literature review.

Bloodstream infection caused by anaerobic microorganisms continues to be associated with a high mortality risk, necessitating a rapid diagnosis and an appropriate treatment. As an anaerobic gram-positive organism associated with vaginal infections, Fannyhessea vaginae is a rare cause of invasive infections. In this case, a 32-year-old pregnant woman with bacterial vaginosis presented with bacteremia. The microbiological analysis of the blood cultures identified F. vaginae. The patient was treated empirically with 5 days of cefoperazone/sulbactam and recovered well. Here, we provide a review of the literature on F. vaginae infections, and the reported cases demonstrate the need for awareness of the different anaerobic species found in the vaginal tract and adaptation of empirical therapies, especially in pregnant women.

Use of probiotic lactobacilli in the treatment of vaginal infections: In vitro and in vivo investigations.

The vaginal microbiome is a distinct component of the human microbiome that is colonized by a wide variety of microorganisms. Lactobacilli are the most frequently identified microorganisms in the healthy human vagina. These Gram-positive bacilli can acidify the vaginal microenvironment, inhibit the proliferation of other pathogenic microorganisms, and promote the maintenance of a eubiotic vaginal microbiome. However, a vaginal flora with a reduced proportion or abundance of lactobacilli is associated with various vaginal infections that have been linked to serious health consequences such as infertility, preterm birth, pelvic inflammatory disease, premature rupture of membranes, and miscarriage. Due to their "Generally Recognized as Safe" classification and critical role in vaginal health, probiotic lactobacilli have been widely used as an alternative or adjunct to traditional antibiotic therapy for the treatment of vaginal infections and restoration of the vaginal microbiome. This review focuses on the significant role of probiotic lactobacilli in the vaginal microenvironment and discusses the use of probiotic lactobacilli in the treatment of female vaginal infections in vitro and in vivo.

Antibiotic resistance and pathogenicity assessment of various Gardnerella sp. strains in local China.

Gardnerella overgrowth is the primary cause of bacterial vaginosis (BV), a common vaginal infection with incidences as high as 23-29% worldwide. Here, we studied the pathogenicity, drug resistance, and prevalence of varying Gardnerella spp. We isolated 20 Gardnerella strains from vaginal samples of 31 women in local China. Ten strains were then selected via phylogenetic analysis of cpn60 and vly gene sequences to carry out genome sequencing and comparative genomic analysis. Biofilm-formation, sialidase, and antibiotic resistance activities of the strains were characterized. All strains showed striking heterogeneity in genomic structure, biofilm formation and drug resistance. Two of the ten strains, JNFY3 and JNFY15, were classified as Gardnerella swidsinskii and Gardnerella piotii, respectively, according to their phenotypic characteristics and genome sequences. In particular, seven out of the ten strains exhibited super resistance (≥ 128 µg/mL) to metronidazole, which is the first line of treatment for BV in China. Based on the biochemical and genomic results of the strains, we proposed a treatment protocol of prevalent Gardnerella strains in local China, which provides the basis for accurate diagnosis and therapy.

miR-26b-5p suppresses chemoresistance in breast cancer by targeting serglycin.

Chemoresistance is a crucial barrier to limit the therapeutic outcome of breast cancer (BC), and the mechanism underlying chemoresistance development in BC is not fully understood. In this study, we aimed to investigate the potential involvement of miR-26b-5p/serglycin (SRGN) axis in BC drug resistance. The expression level of SRGN in drug-resistant BC cells was investigated by western blotting analysis, real-time quantitative PCR (qRT-PCR), immunohistochemical staining, and ELISA. Its expression between chemoresistant and sensitive patient samples was compared by qRT-PCR. Bioinformatics tool and dual-luciferase reporter assay were employed to identify miR-26b-5p as a regulator of SRGN. Functional assays were performed to examine cell proliferation, cell viability, apoptosis, migration, and invasion ability in vitro. Xenograft tumorigenesis experiment was conducted to evaluate the tumor suppressor effect of miR-26b-5p on chemoresistant BC cells. SRGN expression was significantly upregulated in both chemoresistant BC cell lines and chemoresistant patient samples. miR-26b-5p was identified as an upstream regulator of SRGN. Overexpression of miR-26b-5p downregulated SRGN expression, overcame chemoresistance, and suppressed cell proliferation, migration, and invasion in BC cells. Overexpression of miR-26b-5p also suppressed the tumorigenesis of chemoresistant BC cells in vivo. Mechanistically, the downregulation of SRGN by miR-26b-5p decreased the expression of breast cancer drug-resistant protein and multidrug-resistant protein 1 in chemoresistant BC cells. Our study identified miR-26b-5p as a tumor suppressor which targets SRGN to sensitize BC cells to chemotherapeutics. These results suggest that miR-26b-5p and SRGN may serve as potential biomarkers and targets for BC chemotherapy.

LncRNA OTUD6B-AS1 promotes paclitaxel resistance in triple negative breast cancer by regulation of miR-26a-5p/MTDH pathway-mediated autophagy and genomic instability.

Genomic instability (GIN) is pivotal in regulating tumor drug resistance, which blocked the treatment of triple negative breast cancer (TNBC). Although recent studies implied that non-coding RNA (ncRNA)-mediated autophagy abolishment promoted tumorigenesis by up-regulation of GIN, autophagy was known as a risk factor in tumor drug resistance. However, previous study also pointed that up-regulation of autophagy promoted GIN. Therefore, the relationship between autophagy and GIN is not clear, and more work is needed. And, if an ncRNA is identified to be a co-regulator of autophagy and GIN, it will be a potential therapy target of chemotherapy resistance in TNBC. In our study, we recognized both autophagy-GIN-associated microRNA (mi-26a-5p) by big data analysis, which was prognosis-correlated in breast cancer. Next, we identified the up-stream regulators (long non-coding RNA, lncRNA) and down-stream targets of miR-26a-5p by bioinformatics analysis (online public databases). Finally, we established lncRNA OTUD6B-AS1/miR-26a-5p/MTDH signaling pathway, and verified their functions by cytological, molecular biological and zoological experiments. In general, our study found (1) miR-26a-5p was a protective factor of breast cancer, while OTUD6B-AS1 and MTDH were risk factors; (2) OTUD6B-AS1 was the up-stream regulator of miR-26a-5p verified by luciferase; (3) up-regulation of miR-26a-5p and down-regulation of MTDH promoted cellular cytotoxicity of paclitaxel (PTX) in vitro and in vivo. (4) down-regulation of miR-26a-5p, overexpression of MTDH and OTUD6B-AS1 promoted autophagy and DNA damage; (5) up-regulation of OTUD6B-AS1 and MTDH inhibited DNA damage response (DDR) by inhibiting the phosphorylated activation of RAD51, ATR and ATM.

The Female Vaginal Microbiome in Health and Bacterial Vaginosis.

The vaginal microbiome is an intricate and dynamic microecosystem that constantly undergoes fluctuations during the female menstrual cycle and the woman's entire life. A healthy vaginal microbiome is dominated by Lactobacillus which produce various antimicrobial compounds. Bacterial vaginosis (BV) is characterized by the loss or sharp decline in the total number of Lactobacillus and a corresponding marked increase in the concentration of anaerobic microbes. BV is a highly prevalent disorder of the vaginal microbiota among women of reproductive age globally. BV is confirmed to be associated with adverse gynecologic and obstetric outcomes, such as sexually transmitted infections, pelvic inflammatory disease, and preterm birth. Gardnerella vaginalis is the most common microorganism identified from BV. It is the predominant microbe in polymicrobial biofilms that could shelter G. vaginalis and other BV-associated microbes from adverse host environments. Many efforts have been made to increase our understanding of the vaginal microbiome in health and BV. Thus, improved novel and accurate diagnosis and therapeutic strategies for BV have been developed. This review covers the features of vaginal microbiome, BV, BV-associated diseases, and various strategies of diagnosis and treatment of BV, with an emphasis on recent research progresses.

Bioadsorbents from algae residues for heavy metal ions adsorption: chemical modification, adsorption behaviour and mechanism.

Biosorption is an emerging technology for the removal of heavy metals from industrial wastewater by natural or modified biomass. In this study, we proposed a novel protocol for making full use of seaweeds. Brown seaweed Sargassum carpophyllum residue (SCR) and green seaweed Caulerpa lentillifera residue (CLR) were obtained after extraction of the bioactive polysaccharides. The obtained residues were further chemical modified by butanedioic anhydride to obtained respective carboxylated product, named CSCR and CCLR. According to the titration results, CSCR and CCLR contained 2.77 and 2.12 mmol/g of carboxyl group. After modification, the adsorption capacity for metal ions increased by 3-6 times. The adsorption capacity of CSCR for Cu2+, Pb2+, Cd2+ and Mn2+ was 52.37, 107.11, 85.62, and 43.52 mg/g, and that of CCLR was 78.10, 108.80, 87.30 and 57.80 mg/g, respectively. The adsorption was well described by the pseudo-second-order kinetic model and Langmuir adsorption isotherm equation.

Circular RNA circZFR contributes to papillary thyroid cancer cell proliferation and invasion by sponging miR-1261 and facilitating C8orf4 expression.

In recent years, more and more circular RNAs (circRNAs) have been identified in multiple tissues and cells. Increasing evidences show circRNAs play important roles in human cancers. However, the role of circRNAs in papillary thyroid carcinoma (PTC) remains largely unknown. In this study, we identified a new circRNA circZFR that was significantly upregulated in PTC tissues compared to adjacent normal tissues. Furthermore, circZFR expression level was negatively correlated with clinical severity. We found that circZFR knockdown dramatically inhibited the proliferation, migration and invasion of PTC cells in vitro. Mechanistically, we found circZFR could promote C8orf4 expression via serving as a competing endogenous RNA (ceRNA) of miR-1261 in PTC cells. Rescue assays indicated that restoration of C8orf4 significantly attenuated the inhibitory effects of circZFR knockdown on PTC cell proliferation, migration and invasion. In summary, our findings demonstrated that circRNA circZFR exerted oncogenic roles via regulating miR-1261/C8orf4 axis in PTC, which suggested circZFR might be a potential therapeutic target.

Simple Sample Preparation Method for Direct Microbial Identification and Susceptibility Testing From Positive Blood Cultures.

Rapid identification and determination of the antibiotic susceptibility profiles of the infectious agents in patients with bloodstream infections are critical steps in choosing an effective targeted antibiotic for treatment. However, there has been minimal effort focused on developing combined methods for the simultaneous direct identification and antibiotic susceptibility determination of bacteria in positive blood cultures. In this study, we constructed a lysis-centrifugation-wash procedure to prepare a bacterial pellet from positive blood cultures, which can be used directly for identification by matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF MS) and antibiotic susceptibility testing by the Vitek 2 system. The method was evaluated using a total of 129 clinical bacteria-positive blood cultures. The whole sample preparation process could be completed in <15 min. The correct rate of direct MALDI-TOF MS identification was 96.49% for gram-negative bacteria and 97.22% for gram-positive bacteria. Vitek 2 antimicrobial susceptibility testing of gram-negative bacteria showed an agreement rate of antimicrobial categories of 96.89% with a minor error, major error, and very major error rate of 2.63, 0.24, and 0.24%, respectively. Category agreement of antimicrobials against gram-positive bacteria was 92.81%, with a minor error, major error, and very major error rate of 4.51, 1.22, and 1.46%, respectively. These results indicated that our direct antibiotic susceptibility analysis method worked well compared to the conventional culture-dependent laboratory method. Overall, this fast, easy, and accurate method can facilitate the direct identification and antibiotic susceptibility testing of bacteria in positive blood cultures.

Circular exponential amplification of photoinduced electron transfer using hairpin probes, G-quadruplex DNAzyme and silver nanocluster-labeled DNA for ultrasensitive fluorometric determination of pathogenic bacteria.

The authors describe a fluorometric strategy for the detection of pathogenic bacteria with ultrasensitivity and high specificity. This strategy relies on the combination of target-modulated photoinduced electron transfer (PET) between G-quadruplex DNAzyme and DNA (labeled with silver nanoclusters) along with hairpin probe-based circular exponential amplification. The reaction system involves three hairpin probes (H1, H2 and H3). Probe H1 contains an aptamer against S. Typhimurium and the recognition sequence for nicking endonuclease. It is used to recognize S. Typhimurium and participates in polymerase-catalyzed target recycle amplification and secondary-target recycle amplification. Probe H2 contains an aptamer against hemin and is used to form the G-quadruplex DNAzyme in the presence of hemin and potassium ion. It acts as the electron acceptor and quenches the fluorescence of the labeled DNA. Fluorescence is best measured at excitation/emission wavelengths of 567/650 nm. Probe H3 contains the template sequence for the synthesis of AgNCs and the H2-annealing sequence. Both H2 and H3 are utilized to perform a strand displacement reaction and to achieve PET between G-quadruplex DNAzyme and DNA/AgNCs. To the best of our knowledge, this is the first example of a PET between G-quadruplex DNAzyme and DNA/AgNCs coupled with circular exponential amplification. The assay has an ultra-low detection limit 8 cfu·mL-1 of S. Typhimurium. The assay is rapid, accurate, inexpensive and simple. Hence, the strategy may represent a useful platform for ultrasensitive and highly specific detection of pathogenic bacteria as encountered in food analysis and clinical diagnosis. Graphical abstract The reaction system includes three hairpin probes (H1, H2 and H3), primer probe (P), Phi 29 DNA ploymerase (Phi 29) and nicking endonuclease Nt.AlwI (Nt.AlwI). Phi 29 and Nt.AlwI -assisted signal amplification leads to the recycling of target and produces numerous single stranded-DNAs (S). Strand displacement amplification leads to photoinduced electron transfer (PET) between G-quadruplex DNAzyme and DNA/AgNCs. HAP-based circular exponential amplification of PET results in an ultrasensitive fluorometric assay.

Low-background and visual detection of antibiotic based on target-activated colorimetric split peroxidase DNAzyme coupled with dual nicking enzyme signal amplification.

Herein, we have reported the development of a simple, rapid, and low cost colorimetric method for the detection of antibiotic based on target-activated split peroxidase DNAzyme coupled with dual nicking enzyme signal amplification (NESA). To lower background signal in G-quadruplex DNAzyme-based detection, the two split G-rich parts are caged into two different hairpin probes, respectively, preventing the two parts from assembling into the G-quadruplex structure. By the combination of restriction endonuclease-assisted cleavage reaction with the spilt G-quadruplex probes, target-modulated release of the two split G-rich parts is achieved, affording high specificity of antibiotic detection. Our strategy features with several aspects. First, the less background signal produced by the self-assembly of G-quadruplex in the absence of target is effectively eliminated owing to the pre-blocking of the two split G-rich parts. Second, dual NESA coupled G-quadruplex DNAzyme amplification strategy is integrated with colorimetric assay of antibiotic, which significantly improves the detection sensitivity. Third, peroxidase-mimicking DNAzyme is used as biocatalyst in our reaction system, which can catalyze the oxidation of 2,2' - azino - bis (3 - ethylbenzothiozoline - 6 - sulfonic acid) (ABTS2-) mediated by H2O2 to generate the colored radical anion (ABTS•-), allowing to low cost and visual detection of antibiotic by the naked eye. Under optimized conditions, the results revealed the proposed biosensor exhibits excellent specificity and sensitivity toward kanamycin with a detection limit as low as 14.7 pM. Hence, the target-activated split G-quadruplex DNAzyme and dual NESA-based strategy provides a useful and practical platform for antibiotic residues determination and other analytes detection in bio-analysis.

Fabrication of a blood compatible composite membrane from chitosan nanoparticles, ethyl cellulose and bacterial cellulose sulfate.

A heparin-like composite membrane was fabricated through electrospinning chitosan nanoparticles (CN) together with an ethylcellulose (EC) ethanol solution onto a bacterial cellulose sulfate membrane (BCS). Scanning electron microscopy images revealed that there were no chitosan particles in the obtained composite CN-EC/BCS membranes (CEB), indicating CN had been stretched to nanofibers. X-ray photoelectron spectroscopy verified the existence of -NH2 from chitosan and -SO3 - from BCS on the surface of CEB membranes. Positively charged CN in the electrospinning solution and negatively charged BCS on the collector increased the electrostatic force and the electrospinning ability of the EC was increased. The membrane was hydrophobic, with a water contact angle higher than 120°. CEB membranes expressed good blood compatibility according to the results of coagulation time and platelet adhesion experiments. No platelets adhered on the surface of the CEB membranes. An inflammatory response was investigated according to activation of the macrophages seeded onto the membranes. Macrophages seeded on CEB membranes are not activated after 24 h incubation.

[Association between drinking patterns and injuries in emergency room in three domestic general hospitals].

OBJECTIVE: To determine the association between drinking patterns (the volume of drinking and frequency) and injury type (intentional injury and unintentional traffic injury).
 METHODS: A total of 1 539 patients (age≥18 years), who were treated for the first time in the emergency room within 6 h after the injury, were included. The American National Institute of Health questionnaire was used to investigate the injury type, time point of drinking, drinking volume, and drinking history in the past years and so on. The case-crossover method and logistic regression was used to analyze the data.
 RESULTS: Comparing with the control, people with alcohol consuming 6 h before the injury showed a higher risk of intentional injury (OR=3.63). Comparing with people without drinking in the past year, subjects who drank alcohol more than once in the past year displayed a higher risk of intentional injury (OR=1.986). Comparing with non-drinkers, subjects who drank alcohol 5-11 standard drinks or 12 and more drinks on one occasion in the past year had a higher risk of intentional injury (OR=1.854 or 1.572). Comparing with the non-drinkers, victims who drank alcohol 6 h before injury had a higher risk of unintentional traffic injury (OR=2.091). Comparing with non-drinkers in the past year, subjects who drank alcohol more than once in the past year had a higher risk of unintentional traffic injuries (OR=1.533). Comparing with the non-drinkers, subjects who drank alcohol 6 h before injury had a higher risk of injury (OR=5.15). Subjects who drank Less than 6 standard drinks, 6-9 standard drinks and more than 9 standard drinks of alcohol 6 h separately before injury had higher risk than non-drinkers (OR=3.83, 8.64 or 9.58). 
 CONCLUSION: Drinking alcohol before injury is associated with higher risk of intentional injury and unintentional traffic injury. Over the past year, subjects who drank alcohol at least once have higher risk of intentional injuries and unintentional traffic injury. Drinking alcohol 6 h before injury is associated with higher risk of injuries. The risk is increasing with the volume of drinking before injury. The study demonstrates that drinking 6 h before injury and drinking patterns in the past year are closely associated with injuries, which provides scientific evidences for making policy relevant to alcohol consuming.

Correlation Between Clinical-Pathologic Factors and Long-Term Follow-Up in Young Breast Cancer Patients.

OBJECTIVE: Diagnosis of breast cancer in young patients (≤35) correlates with a worse prognosis compared to their older counterparts (>35). The aim of this study is to evaluate the relevance of clinical-pathologic factors and prognosis in young (≤35) breast cancer patients. METHODS: One hundred thirty-two patients of operable breast cancer who were younger than 35 are analyzed in this study. They were treated in our hospital between January 2006 and December 2012. Patients are classified into four molecular subtypes based on the immunohistochemical profiles of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and Ki-67. Clinical and pathologic factors have been combined to define a specific classification of three risk levels to evaluate the prognosis of these young women. RESULTS: Patients whose ages are less than 30 have poorer prognosis than patients whose ages are between 31 and 35. The status of lymph nodes post-surgery seems to be the only factor related to patient age in young patients. The patients in level of ER+ or PR+ and HER2-/+ status have the worst prognosis in hormone receptor-positive breast cancer. Group 3 in risk factor grouping has the poorer prognosis than the other two groups. CONCLUSIONS: Patient age and axillary lymph nodes post-surgery are the independent and significant predictors of distant disease-free survival, local recurrence-free survival, and overall survival. The absence of PR relates to poor prognosis. The risk factor grouping provides a useful index to evaluate the risk of young breast cancer to identify subgroups of patients with a better prognosis.

Evaluation of the pathological response and prognosis following neoadjuvant chemotherapy in molecular subtypes of breast cancer.

BACKGROUND: The pathological complete response of neoadjuvant chemotherapy for breast cancer correlates with the prognosis for survival. Tumors may have different prognoses according to their molecular subtypes. This study was performed to evaluate the relevance of the pathological response and prognosis following neoadjuvant chemotherapy in the molecular subtypes of breast cancer. METHODS: A consecutive series of 88 patients with operable breast cancer treated with neoadjuvant chemotherapy was analyzed. Patients were classified into four molecular subtypes based on the immunohistochemistry profile of the estrogen receptor, progesterone receptor, HER2, and Ki-67. The histological response was assessed according to Miller-Payne grading (MPG) and Residual Disease in Breast and Nodes (RDBN). RESULTS: Ten patients (11.4%) achieved a pathological complete response, assessed according to RDBN. The pathological complete response rate was 13.6% according to MPG. Patients with the triple-negative subtype were more likely to achieve a pathological complete response than those with luminal A breast cancer (P=0.03). MPG and RDBN are independent predictors of distant disease-free survival and local recurrence-free survival, but do not predict overall survival. Ki-67, size of invasive carcinoma, lymph nodes, molecular subtypes, MPG, and RDBN are important predictors of distant disease-free survival, local recurrence-free survival, and overall survival. CONCLUSION: MPG and RDBN were similarly related to the patient's prognosis. MPG was more suitable for evaluation of distant disease-free survival, and RDBN was more suitable for evaluation of local recurrence-free survival. Survival following neoadjuvant chemotherapy correlated with the pathological reaction rather than the molecular subtype of breast cancer. The molecular subtype of breast cancer was not correlated with pathological response in patients who did not achieve a pathological complete response.

Enhanced NK cell adoptive antitumor effects against breast cancer in vitro via blockade of the transforming growth factor-ß signaling pathway.

Natural killer (NK) cells have great potential for improving cancer immunotherapy. Adoptive NK cell transfer, an adoptive immunotherapy, represents a promising nontoxic anticancer therapy. However, existing data indicate that tumor cells can effectively escape NK cell-mediated apoptosis through immunosuppressive effects in the tumor microenvironment, and the therapeutic activity of adoptive NK cell transfer is not as efficient as anticipated. Transforming growth factor-beta (TGF-ß) is a potent immunosuppressant. Genetic and epigenetic events that occur during mammary tumorigenesis circumvent the tumor-suppressing activity of TGF-ß, thereby permitting late-stage breast cancer cells to acquire an invasive and metastatic phenotype in response to TGF-ß. To block the TGF-ß signaling pathway, NK cells were genetically modified with a dominant-negative TGF-ß type II receptor by optimizing electroporation using the Amaxa Nucleofector system. These genetically modified NK cells were insensitive to TGF-ß and resisted the suppressive effect of TGF-ß on MCF-7 breast cancer cells in vitro. Our results demonstrate that blocking the TGF-ß signaling pathway to modulate the tumor microenvironment can improve the antitumor activity of adoptive NK cells in vitro, thereby providing a new rationale for the treatment of breast cancer.