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Levosimendan and dobutamine are extensively used to treat sepsis-associated cardiovascular failure in ICU. Nevertheless, the role and mechanism of levosimendan in patients with sepsis-induced cardiomyopathy remains unclear. Moreover, previous studies on whether levosimendan is superior to dobutamine are still controversial. More importantly, these studies did not take changes (before-after comparison to the baseline) in quantitative parameters such as ejection fraction into account with the baseline level. Here, we aimed to determine the pros and cons of the two medicines by assessing the changes in cardiac function and blood lactate, mortality, with the standardized mean difference used as a summary statistic. Relevant studies were obtained by a thorough and disciplined literature search in several notable academic databases, including Google Scholar, PubMed, Cochrane Library and Embase until November 2020. Outcomes included changes in cardiac function, lactic acid, mortality and length of hospital stay. A total of 6 randomized controlled trials were included in this study, including 192 patients. Compared with dobutamine, patients treated with levosimendan had a greater improvement of cardiac index (ΔCI) (random effects, SMD = 0.90 [0.20,1.60]; I2 = 76%, P 2 = 65%, P = 0.04), a significant decrease of blood lactate (Δblood lactate) (random effects, MD = − 0.79 [− 1.33, − 0.25]; I2 = 68%, P 2 = 0%, P = 0.99). We combine effect sizes related to different measurement parameters to evaluate cardiac function, which implied that septic patients with myocardial dysfunction might have a better improvement of cardiac function by levosimendan than dobutamine (random effects, SMD = 1.05 [0.69,1.41]; I2 = 67%, P

Patients with heart disease often suffer from ischemia, which can be treated by reperfusion. However, this treatment can lead to the development of ischemia/reperfusion (I/R) injury, an inflammatory condition that can cause further heart damage. Dexmedetomidine (Dex), an α2-adrenoceptor agonist, and the microRNA (miR)-17-3p, have both been suggested to alleviate I/R injury and cardiac tissue inflammation. The aim of the present study was to investigate whether Dex and miR-17-3p could act together to prevent I/R injury. H9C2 cells, a myoblast cell line used as a model of rat cardiomyocytes, were cultured in a hypoxic environment for 3 h, and then reoxygenated for 3 h. This hypoxia/reoxygenation (H/R) was used to model I/R. Cell Counting kit-8 was used to determine cell viability and an annexin V-FITC/propidium iodide apoptosis kit used to analyze cell apoptosis. A dual luciferase reporter assay was used to determine the interaction between miR-17-3p and toll-like receptor 4 (TLR4). Western blotting and reverse transcription-quantitative PCR were used to determine protein levels and mRNA expression of TLR4 and galectin-3. A concentration of 0.1-10 µmol/l Dex attenuated H/R injury, which was accompanied by increased miR-17-3p levels. Additionally, the inhibition of miR-17-3p exacerbated H/R injury and reduced the effect of Dex on H/R injury. H/R led to an increased galectin-3 level compared with that in control cells, and Dex or miR-17-3p inhibitor did not markedly affect the level of galectin-3, indicating that Dex alleviated the effects of I/R injury through other pathways. Inhibition of miR-17-3p in Dex-induced H9C2 cells during H/R increased the expression of inflammatory mediators including tumor necrosis factor-α, interleukin (IL)-6, IL-1β and phosphorylated NFκB subunit p65, while Dex reduced the H/R-induced expression of these inflammatory mediators. Inhibition of TLR4 also attenuated H/R injury. In summary, the findings of the present study indicated that Dex reduced H/R injury in H9C2 cell via the modulation of inflammatory signaling pathways, and these inflammatory factors could be regulated by miR-17-3p.

Simple Summary The present study aimed to investigate a lethal outbreak of chlamydiosis and pigeon circovirus (PiCV) infection in a zoo. A retrospective follow-up indicates that the lethal outbreak might be an independent episode. The high prevalence of PiCV positivity in the aviaries suggests that PiCV infection might play a key role in augmenting the lethality of chlamydiosis in birds. Persistently monitoring both pathogens and identifying potential PiCV carriers or transmitters might also help prevent lethal disease outbreaks. Abstract During the spring, an outbreak of sudden death involving 58 birds occurred in a zoo. Histopathological examinations revealed variable numbers of intracytoplasmic basophilic microorganisms in the macrophages, hepatocytes, and renal epithelium of most birds, along with occasional botryoid intracytoplasmic inclusion bodies within histiocytes in the bursa of Fabricius. Based on the results of histopathological examinations, immunohistochemical staining, transmission electron microscopy, and polymerase chain reactions, genotype B Chlamydia psittaci infection concurrent with pigeon circovirus (PiCV) was diagnosed. A retrospective survey, including two years before the outbreak and the outbreak year, of C. psittaci and PiCV infections of dead birds in the aviaries, revealed that the outbreak was an independent episode. The findings of this study indicate that concurrent infection with C. psittaci and PiCV might lead to lethal outbreaks of chlamydiosis, particularly Streptopelia orientalis. In addition, persistently monitoring both pathogens and identifying potential PiCV carriers or transmitters might also help prevent lethal disease outbreaks.

Papillomaviruses (PVs) usually cause benign proliferative lesions in the stratified epithelium of various animal species. However, some high-risk types of PVs have been proven to lead to malignant transformations. In dogs, several canine papillomaviruses (CPVs) have been identified in malignant lesions and are suggested as one of the risk factors for the development of squamous cell carcinomas (SCCs). In the present study, the full genomes of two CPV9 strains from recurrent SCCs of Dog 1 and skin viral papilloma (viral plaque) of Dog 2 were sequenced. Alignment of the two CPV9 sequences with the genome of the reference CPV9 strain (accession no. JF800656.1) derived from a solitary pigmented plaque was performed. Compared with the reference strain, a 27 bp in-frame insertion in the E1 gene was identified in both CPV9 strains in this study. In comparison with the CPV9 strains derived from benign lesions, the CPV9 from the SCCs of Dog 1 exhibited a 328 bp deletion at the 3′ end of the E2 and spacer sequence, which encoded a truncated deduced E2 protein and a chimeric E8^E2 protein. However, there was no difference in the mRNA expression levels of viral oncoproteins of E6 and E7 between the two CPV9 cases, suggesting that the oncogenesis of CPV9 for malignant transformation might be different from that of human papillomaviruses. The roles of E2 and E8^E2 deleted CPV9 in the oncogenesis of benign and malignant lesions should be further investigated.

Papillomavirus (PV) mainly infects the squamous epithelium and may potentially lead to benign or even malignant cutaneous lesions. However, the malignant transforming ability has been identified in several types of PVs. In humans, papillomavirus (HPV) type 16 and 18 are the most prevalent causative agents of cervical cancer. Therefore, vaccines are being developed to protect against these types. For dogs, there have been limited investigations into the association of different canine papillomavirus (CPV) genotypes with malignant lesions. Understanding the high-risk CPV genotype(s) responsible for these malignant lesions would contribute to the development of interventions for preventing CPV-induced carcinomas. In the present study, a retrospective cohort of 102 pathologically confirmed papillomas and 212 squamous cell carcinomas (SCCs) were included. The viral genome and antigens in the formalin-fixed paraffin-embedded (FFPE) tissues were detected using PCR targeting pan PV E1 and COPV L1 genes and by immunohistochemistry staining (IHC), respectively. PVs were successfully detected from 11 FFPE cutaneous tissues and four oral tissues using pan PV E1- and COPV L1-based PCR, respectively. After sequencing, CPV 1, CPV 2, and CPV 6 were detected in the benign lesions using PCR and were confirmed through IHC. While CPV 9 and CPV 15 were first detected in the SCCs of dogs, CPV 16 was most often detected in SCC specimens. The association and confirmative demonstration of viral genes and intralesional antigens of CPV 9, CPV 15, and CPV 16 in SCCs highlight the potential risk of these genotypes of CPVs in malignant transformation.

BACKGROUND Sepsis-induced myopathy (SIM) is a complication of sepsis that results in prolonged mechanical ventilation, long-term functional disability, and increased patient mortality. This study aimed to use bioinformatics analysis to identify hub genes and molecular pathways involved in SIM, to identify potential diagnostic or therapeutic biomarkers. MATERIAL AND METHODS The Gene Expression Omnibus (GEO) database was used to acquire the GSE13205 expression profile. The differentially expressed genes (DEGs) in cases of SIM and healthy controls, and the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed using the limma R/Bioconductor software package and clusterProfiler package in R, respectively. The protein-protein interaction (PPI) network data of DEGs was retrieved using the STRING database and analyzed using the Molecular Complex Detection (MCODE) Cytoscape software plugin. RESULTS A total of 196 DEGs were obtained in SIM samples compared with healthy samples, including 93 upregulated genes. The DEGs were significantly upregulated in mineral absorption, and the interleukin-17 (IL-17) signaling pathway and 103 down-regulated genes were associated with control of the bile secretion signaling pathway. A protein-protein interaction (PPI) network was constructed with 106 nodes and 192 edges. The top two important clusters were selected from the PPI by MCODE analysis. There were 16 hub genes with a high degree of connectivity in the PPI network that were selected, including heme oxygenase 1 (HMOX1), nicotinamide adenine dinucleotide phosphate quinone dehydrogenase 1 (NQO1), and metallothionein (MT)-1E. CONCLUSIONS Bioinformatics network analysis identified key hub genes and molecular mechanisms in SIM.

Background: Sepsis-induced myopathy (SIM) is a disease that causes motor dysfunction in patients with sepsis. There is currently no targeted treatment for this disease. Acupuncture has shown considerable efficacy in the treatment of sepsis and muscle weakness. Therefore, our research aims to explore the effects of acupuncture on the improvement of muscle structure and function in SIM patients and on activities of daily living. Methods: The ACU-SIM pilot study is a single-center, propensity-score stratified, assessor-blinded, prospective pragmatic controlled trial (pCT) with a 1-year follow-up period. This study will be deployed in a multi-professional critical care department at a tertiary teaching hospital in Guangzhou, China. Ninety-eight intensive care unit subjects will be recruited and assigned to either the control group or the acupuncture group. Both groups will receive basic treatment for sepsis, and the acupuncture group will additionally receive acupuncture treatment. The primary outcomes will be the rectus femoris cross-sectional area, the Medical Research Council sum-score and time-to-event (defined as all-cause mortality or unplanned readmission to the intensive care unit due to invasive ventilation). The activities of daily living will be accessed by the motor item of the Functional Independence Measure. Recruitment will last for 2 years, and each patient will have a 1-year follow-up after the intervention. Discussion: There is currently no research on the therapeutic effects of acupuncture on SIM. The results of this study may contribute to new knowledge regarding early muscle atrophy and the treatment effect of acupuncture in SIM patients, and the results may also direct new approaches and interventions in these patients. This trial will serve as a pilot study for an upcoming multicenter real-world study. Trial registration: Chinese Clinical Trials Registry: ChiCTR-1900026308, registered on September 29th, 2019.

Hemophagocytic lymphohistiocytosis (HLH) is a rare hyperinflammatory syndrome characterized by fever, pancytopenia and splenomegaly. The underlying hemophagocytosis occurs primarily in the bone marrow, liver and lymph nodes. Multiple microbiological agents, including cytomegalovirus, Epstein-Barr virus and Mycobacterium tuberculosis, have been implicated in the pathogenesis of HLH. The present study presents a case of HLH associated with Leuconostoc pseudomesenteroides infection treated successfully with clindamycin. A 33-year-old man presented with recurrent episodes of fever and diarrhea. Upon initial treatment at another hospital (the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China), blood chemistry analysis demonstrated moderate anemia (hemoglobin 88 g/l; reference range, 120.0–160.0), elevated ferritin (1,068.47 mg/l; reference range, 21.81–274.66), total bilirubin (392.4 mmol/l; reference range, 5.1–28.0), conjugated bilirubin (335.7 mmol/l; reference range, 0–10.0), and γ-glutamyl transpeptidase (150 U/l; reference range, 10–60). The patient was treated with antibiotics for suspected pneumonia and cholecystitis, but new symptoms (including diarrhea and inflammatory colitis) started to emerge. The patient was subsequently treated with ganciclovir (5 mg/kg/day for 1 month), but body temperature increased to 41.0°C. Upon transferring to our hospital, the patient had severe anemia (hemoglobin, 39 g/l; red blood cell, 1.61×1012/l; reference range, 4.0–5.5×1012/l). Jaundice was apparent: Total bilirubin, 299.5 mmol/l; conjugated bilirubin, 215.7 mmol/l. The patient was treated with clindamycin (150 mg, taken orally every 12 h for 1 week) and supportive care that included parenteral nutrition. Symptoms rapidly dissipated after the treatment. Blood chemistry analysis 5 days after the first dose of clindamycin revealed substantial improvement in anemia and jaundice. The patient requested discharge for financial reasons, but continued treatment (details not available) at a local hospital (Pengpai Memorial Hospital, Shanwei, China). Upon a visit to our hospital 8 months later, the patient has no notable complaints, with the exception of moderate anemia. The present case suggests that HLH may be associated with L. pseudomesenteroides infection.