The Epidemiology and Clinical Characteristics of Fungemia in a Tertiary Hospital in Southern China: A 6-Year Retrospective Study.

Knowledge of the epidemiology and clinical characteristics of fungemia in southern China is limited. We conducted a six-year retrospective descriptive study to analyze the epidemiological and clinical characteristics of fungemia at the largest tertiary hospital in Guangxi, southern China. Data were obtained from the laboratory registry of patients with fungemia between January 2014 and December 2019. Demographic characteristics, underlying medical conditions, and outcomes for each case were analyzed. A total of 455 patients with fungemia were identified. Unexpectedly, Talaromyces marneffei (T. marneffei) was the most frequently isolated agent causing fungemia in the region (149/475, 31.4%), and Candida albicans (C. albicans) was the most commonly isolated Candida spp. (100/475, 21.1%). We identified that more than 70% of talaromycosis fungemia developed in AIDS patients, whereas candidemia was most commonly associated with a history of recent surgery. Notably, the total mortality rate of fungemia and the mortality rate in patients with T. marneffei and Cryptococcus neoformans (C. neoformans) fungemia were significantly higher in HIV-uninfected patients than in HIV-infected patients. In conclusion, the clinical pattern of fungemia in Guangxi is different from that in previous studies. Our study may provide new guidance for the early diagnosis and prompt treatment of fungemia in similar geographic regions.

Protocol for integrated analysis of bacterial RNA-seq and ChIP-seq data for establishing a co-expression network.

Transcriptomic data and ChIP-seq data from bacteria are systematically analyzed and efficiently combined. We describe the software environment for analysis and the download and installation methods. Furthermore, we describe the analytical process and present the corresponding mini-test data, which can be conveniently restored and reproduced by users. Moreover, we provide the script for data consolidation, which allows multiple files to be rapidly merged. Overall, this protocol presents software parameters, R codes, and in-house Perl scripts for analyzing bacterial multi-omics data. For complete details on the use and execution of this protocol, please refer to Xin et al.

The Efficacy of Anterior Cervical Corpectomy and Fusion and Posterior Total Laminectomy on Cervical Spinal Cord Injury and Quality of Life.

This study is aimed at investigating the efficacy of anterior cervical corpectomy and fusion and posterior total laminectomy in the treatment of cervical spinal cord injury and assessing the impact of the two approaches on cervical spine function and patient quality of life. Retrospectively analyze the clinical data from 180 patients with cervical spinal cord injury who were admitted to the First Affiliated Hospital of Hebei North University from June 2019 to June 2021. The patients were divided into an anterior approach group (n = 89, treated with anterior cervical corpectomy and fusion) and a posterior approach group (n = 91, treated with posterior total laminectomy). The amount of blood loss in the posterior approach group was larger compared to the anterior approach group. Patients in the posterior approach group had higher wound diameters and operation times compared to the anterior approach group, as well as the operation cost. The visual analogue scale (VAS) scores of patients in the posterior approach group were significantly higher than in the anterior approach group one month after operation. The Japanese Orthopaedic Association (JOA), neck disability index (NDI), and American Spinal Injury Association (ASIA) scores of patients in both groups at 1, 6, and 9 months after surgery were higher compared to those before surgery, yet no significant differences were observed between the two groups. Also, no significant difference was observed in the incidence of complication and the quality of life between the two groups before and after treatment. Anterior cervical corpectomy and fusion and posterior total laminectomy can effectively restore the cervical nerve function in the treatment of cervical spinal cord injury. However, anterior subtotal vertebral resection is associated with improved perioperative indicators compared to posterior total laminectomy. Clinically, surgical methods can be selected according to imaging findings, the general condition of patients, and individual economic status.

Complete Genome Sequences of Four Campylobacter jejuni Strains Isolated from Retail Chicken Meat and Broiler Feces.

Campylobacter jejuni is the leading pathogen that causes foodborne infections. Here, we report the complete genome sequences of four C. jejuni strains isolated from retail chicken meat and broiler feces samples. Genes encoding type VI secretion and antibiotic resistance were detected among these isolates.

Prevalence, Antimicrobial Resistance, and Molecular Characterization of Campylobacter Isolated from Broilers and Broiler Meat Raised without Antibiotics.

Campylobacter is one of the main bacterial pathogens that cause campylobacteriosis in the United States. Poultry is considered a major reservoir for the transmission of Campylobacter to humans. This study aimed to determine the prevalence and molecular characteristics of Campylobacter in the no-antibiotics-ever (NAE) broilers. A total of 414 samples were collected, among which 160 retail chicken samples were purchased from grocery stores and 254 samples were collected from broiler farms located in Mississippi State. The overall prevalence of Campylobacter was 25.4%, and a significantly higher prevalence was observed in retail chicken than in the farm samples (36.3% versus 18.5%; P < 0.0001), respectively. The prevalence of Campylobacter was not different (P = 0.263) between conventional retail (40.0%) and NAE (31.4%) retail chicken. Campylobacter jejuni was the predominant species among the positive isolates, accounting for 78.1%. Among the 82 C. jejuni isolates, 52.4% of the isolates carried the gyrA gene followed by the tet(O) gene (14.6%), whereas toxin-producing genes cdtA, cdtB, and cdtC were carried by 43.9%, 46.3%, and 43.9%, respectively. However, none of these virulence genes were detected in C. jejuni isolated from litter samples. Among tested C. jejuni, 13.6% of the isolates were multidrug resistant. The highest resistance was observed against nalidixic acid (49.2%), followed by tetracycline (23.7%). Our study suggests that the prevalence of Campylobacter was higher in retail meat samples than in environmental samples obtained from farms, and there was no difference in Campylobacter prevalence among conventional and NAE retail chicken. IMPORTANCE The FDA antibiotic withdrawal policy has led to a shift in the production system, from conventional antibiotics fed birds to no antibiotics ever (NAE) raised birds. However, the impact of this shift to NAE on the prevalence and characteristics of Campylobacter has not been studied on the farm or in retail chicken meats. The objective of this study was to determine the current prevalence of Campylobacter and the distribution of their antimicrobial resistance and virulence genes in NAE-raised broilers. The findings of this study will help the industry to take necessary action to develop effective mitigation strategies for reducing Campylobacter contamination in NAE broilers.

LncRNA-mRNA co-expression network revealing the regulatory roles of lncRNAs in melanogenesis in vitiligo.

Vitiligo is characterized by the progressive disappearance of melanocytes, resulting in depigmentation. Long noncoding RNAs (lncRNAs) are a class of noncoding RNAs that play an essential role in the regulation of inflammation and immunity. Published reports on the expression profile of lncRNAs in vitiligo cases and the potential biological function of lncRNAs in vitiligo are lacking. We performed RNA-Seq to identify the functions of lncRNAs in vitiligo. In total, 32 upregulated lncRNAs and 78 downregulated lncRNAs were identified in skin lesions with vitiligo. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis demonstrated that mRNAs regulated by abnormally expressed lncRNAs are most relevant to melanocyte function and melanogenesis. We identified 14 aberrantly expressed lncRNAs through the co-expression pattern that regulate the melanogenesis-related genes DCT, TYR, and TYRP1. Therefore, we speculate that these hub genes may be involved in pathological mechanisms in melanocytes in vitiligo. These genes are closely related to melanogenesis in vitiligo. Abnormally expressed lncRNAs directly or indirectly act on these target genes to regulate melanogenesis. Identifying lncRNAs and clarifying the regulatory roles of the lncRNA-mRNA network may be helpful to develop novel diagnoses or treatment targets for vitiligo.

Synchronized and integrated prehospital treatment for acute cervical spinal cord injury.

OBJECTIVE: To explore the effect of synchronized and integrated prehospital treatment strategies for on-site first aid, rescue transport and prehospital first aid in patients with acute cervical spinal cord injury. METHODS: A prospective non-randomized controlled study was designed to include patients with acute cervical spinal cord injury. A total of 50 patients were included in a Control group (before the implementation of synchronized and integrated prehospital treatment), and 50 patients were included in an Observation Group (after the implementation of synchronized and integrated prehospital treatment). We compared the timeliness of prehospital treatment, the proportion of patients received methylprednisolone treatment within 3 h after injury, the changes in Japanese Orthopaedic Association (JOA) score during transport, the incidence of adverse events, the clinical outcomes, the number of prehospital deaths, the case number of paralysis and the recovery of postoperative neural function between the two groups. RESULTS: Compared with the Control group, the Observation group showed significantly shorter time from injury to admission, from injury to receiving methylprednisolone pulse therapy, as well as from injury to receiving dehydrating agents and diuretics (all P<0.001). The proportion of patients received methylprednisolone treatment within 3 h after injury was significantly higher in the Observation group than that in the Control group (P<0.05). There was no significant change in the JOA score in the Observation group before and after the transport, while the score was significantly lower in the Control group after the transport (P<0.001). The JOA score was higher in the Observation group than that in the Control group at admission (P<0.001). The Observation group also showed decreased incidences of adverse events, mortality, and paralysis rate (all P<0.05) as well as better recovery of postoperative neural function (P<0.001) when compared with the Control group. CONCLUSION: Synchronized and integrated prehospital treatment has a significant effect in patients with acute cervical spinal cord injury through shortening the admission time, reducing the risk of adverse events, and improving the rescue effect and the prognosis of neural function.

Restoring microRNA-499-5p Protects Sepsis-Induced Lung Injury Mice Via Targeting Sox6.

BACKGROUND: MicroRNAs (miRs) are known to participate in sepsis; hence, we aim to discuss the protective effect of miR-499-5p targeting sex-determining region Y-related high-mobility-group box 6 (Sox6) on sepsis-induced lung injury in mice. METHODS: The sepsis-induced lung injury model was established by cecal ligation and puncture. The wet/dry weight (W/D) ratio, miR-499-5p, Sox6, Caspase-3 and Caspase-9 expression in lung tissues of mice were tested. Lung injury score, collagen fibers and the degree of pulmonary fibrosis in lung tissues were determined. Further, the cell apoptosis in lung tissues was measured. The inflammatory factors contents and oxidative stress indices in bronchoalveolar lavage fluid (BALF) and lung tissues were detected via loss- and gain-of-function assays. The targeting relation between miR-499-5p and Sox6 was verified. RESULTS: W/D ratio and Sox6 were increased while miR-499-5p was decreased in lung tissues of sepsis-induced lung injury mice. Restored miR-499-5p or depleted Sox6 alleviated lung tissues pathology, reduced lung injury score, collagen fibers, the degree of pulmonary fibrosis, TUNEL positive cells, Caspase-3 and Caspase-9 protein expression and inflammatory factors contents in BALF and lung tissues as well as oxidative stress response in lung tissues of sepsis-induced lung injury mice. miR-499-5p targeted Sox6. CONCLUSION: High expression of miR-499-5p can attenuate cell apoptosis in lung tissues and inhibit inflammation of sepsis-induced lung injury mice via depleting Sox6, and it is a potential candidate marker and therapeutic target for sepsis-induced lung injury.

Effects of in ovo probiotic administration on the incidence of avian pathogenic Escherichia coli in broilers and an evaluation on its virulence and antimicrobial resistance properties.

Avian pathogenic Escherichia coli (APEC) causes colibacillosis in poultry, which has been traditionally controlled by the prophylactic in-feed supplementation of antibiotics. However, antibiotics are being removed from poultry diets owing to the emergence of multidrug-resistant (MDR) bacteria. Therefore, alternatives to control APEC are required. This study aimed to evaluate the effects of in ovo inoculation of probiotics on the incidence of APEC in broilers and evaluate the virulence and antimicrobial resistance properties of the APEC isolates. On embryonic day 18, 4 in ovo treatments (T) were applied: T1 (Marek's vaccine [MV]), T2 (MV and Lactobacillus animalis), T3 (MV and Lactobacillus reuteri), and T4 (MV and Lactobacillus rhamnosus). A total of 180 male broilers per treatment were randomly placed in 10 pens. The heart, liver, spleen, and yolk sac were collected on day 0, 14, 28, and 42. Presumptive E. coli isolates were confirmed by real-time PCR. The positive isolates were screened for the APEC-related genes (iroN, ompT, hlyF, iss, and iutA), and E. coli isolates containing one or more of these genes were identified as APEC-like strains. A total of 144 APEC-like isolates were isolated from 548 organ samples. No differences (P > 0.05) among treatments were observed for the incidence of APEC-like strains in all organs when averaged over sampling days. However, when averaged over treatments, the incidence in the heart, liver, and yolk sac was different among sampling days; a significant increase was observed in these organs on day 14 compared with day 0. Twenty-five antimicrobial resistance genes were evaluated for all APEC-like isolates, and 92.4% of the isolates carried at least one antimicrobial resistance gene. Thirty-seven isolates were then selected for antimicrobial susceptibility testing; MDR strains accounted for 37.8% of the isolates. In conclusion, the in ovo inoculation of a single probiotic strain did not confer protection against APEC strains in broilers. The high prevalence of MDR isolates indicates that further research on antibiotic alternatives is required to prevent APEC infections in broilers.

Complete genome sequence of multidrug-resistant avian pathogenic Escherichia coli strain APEC-O2-MS1170.

OBJECTIVES: Avian pathogenic Escherichia coli (APEC) causes colibacillosis, one of the leading causes of mortality and morbidity associated with significant economic losses in the poultry industry. This study aimed to determine antimicrobial resistance and to characterise the genome sequence of a multidrug-resistant (MDR) APEC strain isolated from a broiler chicken. METHODS: Strain APEC-O2-MS1170 was isolated from the broiler yolk sac of a 14-day-old broiler. Antimicrobial susceptibility testing was performed using a Sensititre National Antimicrobial Resistance Monitoring System (NARMS) Gram-negative panel. Whole-genome sequencing was performed using both the long-read sequencing approach with a Nanopore GridION sequencer and short-read sequencing with an Illumina HiSeq X-Ten sequencer to obtain a complete scaffold of the genome and an accurate sequence. RESULTS: The genome size of strain APEC-O2-MS1170 is 4,993,909 bp with a GC content of 50.7% and 4,651 protein-coding sequences. Public databases were used to identify the virulence-associated gene and antimicrobial resistance gene cargo. Plasmid comparison showed that pAPEC-O2-MS1170-R is a large multidrug resistance IncB/O/K/Z plasmid, while pAPEC-O2-MS1170-ColV shares homology with the APEC ColV virulence plasmid. CONCLUSION: The genome sequence of APEC-O2-MS1170 provides valuable information on resistance mechanisms and virulence characteristics of pathogenic E. coli as well as information for tracing the potential spread of this MDR strain.

Therapeutic effects of interleukin-37 and induced cardiosphere on treating myocardial ischemia-reperfusion injury.

BACKGROUNDS: Myocardial ischemia-reperfusion injury (MI-RI) has many adverse complications with high mortality rate. In the current study, we investigated the therapeutic advantages of delivering Interleukin-37 (IL-37) by induced cardiospheres (iCS), generated from adult skin fibroblasts via somatic reprogramming, in treating the mice model MI-RI. METHODS: The mouse model of MI-RI was established and the iCS cells with IL-37 overexpression (iCS-IL37) were transplanted into the mice via tail-vein injection. Left ventricular (LV) dimensions and LV pressure-volume measurements were assessed by parasternal long-axis echocardiography and hemodynamic assessment. The infarct size was determined by histology analysis. And the inflammatory responses were analyzed by using enzyme-linked immunosorbent assay (ELISA). RESULTS: The LV function was significantly improved after the iCS-IL37 transplantation when compared to the vehicle control group and iCS group, including the end-systolic pressure and dP/dtMax. Furthermore, the infarct size was significantly decreased after the iCS-IL37 transplantation. The protein levels of pro-inflammatory cytokines, including tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß), were down-regulated by the iCS-IL37 transplantation. CONCLUSION: The present study indicated that the iCS with IL-37 overexpression had therapeutic effects on the mice model of MI-RI.

Anti-IFN-γ autoantibodies underlie disseminated Talaromyces marneffei infections.

Talaromyces marneffei causes life-threatening opportunistic infections, mainly in Southeast Asia and South China. T. marneffei mainly infects patients with human immunodeficiency virus (HIV) but also infects individuals without known immunosuppression. Here we investigated the involvement of anti-IFN-γ autoantibodies in severe T. marneffei infections in HIV-negative patients. We enrolled 58 HIV-negative adults with severe T. marneffei infections who were otherwise healthy. We found a high prevalence of neutralizing anti-IFN-γ autoantibodies (94.8%) in this cohort. The presence of anti-IFN-γ autoantibodies was strongly associated with HLA-DRB1*16:02 and -DQB1*05:02 alleles in these patients. We demonstrated that adult-onset acquired immunodeficiency due to autoantibodies against IFN-γ is the major cause of severe T. marneffei infections in HIV-negative patients in regions where this fungus is endemic. The high prevalence of anti-IFN-γ autoantibody-associated HLA class II DRB1*16:02 and DQB1*05:02 alleles may account for severe T. marneffei infections in Southeast Asia. Our findings clarify the pathogenesis of T. marneffei infection and pave the way for developing novel treatments.

Analysis of Severe Fever With Thrombocytopenia Syndrome in Critical Ill Patients in Central China.

INTRODUCTION: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging zoonosis infected by virus (SFTSV) in central and eastern China, which is associated with high mortality. However, limited clinical data have been reported about this critical illness. PATIENTS AND METHODS: Retrospective cohort study in intensive care unit (ICU) patients with SFTSV infection admitted in 2014 to 2019. Diagnosis was confirmed using reverse transcription polymerase chain reaction on serum samples. RESULTS: One hundred sixteen patients with SFTSV infection were included (mean age 63 ±â€Š9 years, 59 [51.3%] males). Non-survivors (43.1%) were older, and had lower Glasgow Coma Score, higher Acute Physiology and Chronic Health Evaluation II, and sequential organ failure assessment score at ICU admission. In addition, non-survivors had more severe respiratory failure (PaO2/FiO2: 208 ±â€Š14 mm Hg vs. 297 ±â€Š15 mm Hg), more frequent shock (25[50%] vs. 7[10.6%]), and required more frequently mechanical ventilation (78% vs. 19.7%; P < 0.001) and vasopressor support (56% vs. 9.1%; P < 0.001). Non-survivors experienced more obvious monocyte loss. After adjustment for potential confounding factors, older age, elevated lactate level, and elevated creatinine level were the independent risk factors for death. CONCLUSION: We provided knowledge about the clinical characteristics of SFTS admitted in ICU. Older age, elevated lactate level, and elevated creatinine level may be useful for identifying patients with poor outcome and intensive medical intervention can be provided for patients as soon as possible to reduce mortality.

Characteristics and Prognosis of Talaromyces marneffei Infection in Non-HIV-Infected Children in Southern China.

Knowledge about the clinical and laboratory characteristics and prognosis of Talaromyces marneffei infection in children is limited. A retrospective study was conducted on pediatric patients with disseminated T. marneffei infection in a clinical setting. Extracted data included demographic information (age and sex), clinical features, laboratory findings, treatment, and prognosis. Eleven HIV-negative children were enrolled. The male/female ratio was 8:3. The median age of onset was 17.5 months (3.5-84 months). The mortality rate in these children was 36.36% (4/11). Seven children had underlying diseases. All of the children had multiple immunoglobulin abnormalities and immune cell decline. Ten children received voriconazole treatment, and most of the children (7/10) had a complete response to therapy at primary and long-term follow-up assessment; only three children died of talaromycosis. One patient recovered from talaromycosis but died of leukemia. The child who received itraconazole treatment also showed clinical improvement. No adverse events associated with antifungal therapies were recorded during and after the treatment. Talaromycosis is an indicator disease for undiagnosed severe immunodeficiencies in children. Awareness of mycoses in children by pediatricians may prompt diagnosis and timely treatment. Voriconazole is an effective, well-tolerated therapeutic option for disseminated T. marneffei infection in non-HIV-infected children.

In Vitro Susceptibility of Berberine Combined with Antifungal Agents Against the Yeast Form of Talaromyces marneffei.

Talaromyces (Penicillium) marneffei can cause fatal disseminated infection in immunocompromised hosts. However, therapeutic strategies for the mycosis are limited. Reports of the other fungi suggest that berberine, a component of traditional herb, inhibitors interact with antifungal agents to improve the treatment outcomes. In the study, we evaluated the in vitro efficacy of berberine in combination with conventional antifungal agents against the pathogenic yeast form of T. marneffei. We demonstrate the synergistic effect of combination of berberine with fluconazole (52.38%), itraconazole (66.67%), voriconazole (71.43%), amphotericin B (71.43%) or caspofungin (52.38%) of T. marneffei strains, respectively. Time-kill curves confirmed the synergistic interaction, and no antagonistic was observed in all of the combinations. In conclusion, berberine could enhance the efficacy of conventional antifungal agents against the yeast form of T. marneffei in vitro. The results indicated berberine might have a potential role in combination therapy for talaromycosis.

Determination of anethole trithione in human plasma using high performance liquid chromatography coupled with tandem mass spectrometric detection.

A rapid, sensitive and reliable high performance liquid chromatographic method coupled with tandem mass spectrometry via electrospray ionization (ESI) source (HPLC-MS/MS) has been developed and validated for the determination of anethole trithione (ATT) in human plasma. Diazepam was employed as the internal standard (IS). Sample extracts following liquid-liquid extraction were injected into the HPLC-MS/MS system. The analyte and IS were eluted isocratically on a C18 column, with a mobile phase consisting of methanol and aqueous ammonium acetate solution (5 mM) (80:20, v/v) . The ions were detected by a triple quadrupole mass spectrometric detector in the positive mode. Quantification was performed using selected reaction monitoring (SRM) of the transitions m/z 240.88-->197.91 and m/z 285.01-->193.02 for ATT and for the IS, respectively. The analysis time for each run was 5.0 min. The calibration curve fitted well over the concentration range of 0.02-5 ng mL(-1), with the regression equation y = 1.1014x + 0.0003631, r = 0.9992. The intra-batch and inter-batch R.S.D.% were less than 15% at all concentration levels within the calibration range. The recoveries were more than 80%. The present method provides a modern, rapid and robust procedure for the pharmacokinetic study of ATT. Some important pharmacokinetic parameters of ATT in healthy Chinese volunteers are also given for the first time.