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1.
Infect Drug Resist ; 17: 1003-1010, 2024.
Article in English | MEDLINE | ID: mdl-38500637

ABSTRACT

Background: Chromobacterium violaceum (C. violaceum) is a Gram-negative bacterium capable of causing severe infections in both humans and specific animals. Despite its infrequency, C. violaceum infections exhibit a notably high mortality rate. The timely and precise detection of this pathogen stands as a critical factor in achieving effective diagnosis and treatment. Traditional diagnostic approaches possess limitations, particularly in terms of their time-consuming nature and the range of pathogens they can identify. Metagenomic next-generation sequencing (mNGS) testing has emerged as a highly promising diagnostic tool for infectious diseases. Methods: Within this case report, we present a patient who developed a C. violaceum infection subsequent to a lower limb infection, leading to the progression of sepsis, a liver abscess, septic shock, multi-organ dysfunction, and altered mental status. Samples of the patient's blood and tissue from the lower limb skin are collected, and the infection is swiftly diagnosed through mNGS, allowing for the immediate initiation of suitable treatment. Results: The mNGS results revealed the patient's infection with C. violaceum. Subsequent conventional bacterial culture results were concordant with the mNGS findings. Following comprehensive management measures, including prompt and effective anti-infective treatment, the patient achieved cure and was successfully discharged. Conclusion: This case underscores the significance of employing advanced diagnostic methodologies like mNGS for the early detection of uncommon pathogens such as C. violaceum. The expedited diagnosis and timely intervention hold the potential to substantially enhance patient outcomes in cases of severe infections instigated by this bacterium.

2.
Int J Antimicrob Agents ; 63(5): 107152, 2024 May.
Article in English | MEDLINE | ID: mdl-38513747

ABSTRACT

INTRODUCTION: Ceftazidime-avibactam (CAZ-AVI) is a new option to treat KPC- and OXA-48 carbapenem-resistant Klebsiella pneumoniae (CRKP) infections. However, clinical evidence is limited regarding its use in treating CRKP infections, especially in solid organ transplantation (SOT) recipients. In this study, we assessed the efficacy of CAZ-AVI in treating CRKP infections in both the general population and the SOT recipients in comparison with other antibiotic regimens. METHODS: This is a single-centre retrospective cohort study of patients admitted between January 1, 2018 and June 30, 2021 with the diagnosis of CRKP infections receiving either CAZ-AVI or other regimens ≥ 72 hours and clinical outcomes were analysed. RESULTS: Of 200 patients with CRKP infections, 67 received CAZ-AVI, 133 received other regimens, and 50 were SOT recipients. In the SOT cohort, 30 patients received CAZ-AVI, and 20 received other regimens. The overall 30-day mortality was 38% in the SOT cohort. Compared with patients receiving other regimens, CAZ-AVI therapy resulted in lower 30-day mortality (23.3% vs. 60%, P = 0.014) and 90-day mortality (35.7% vs. 86.7%, P = 0.003), higher clinical cure (93.3% vs. 40%, P < 0.001) and microbiological clearance. Similar promising results of CAZ-AVI were also shown in the whole population cohort. Moreover, clinical outcomes of SOT recipients receiving CAZ-AVI were not inferior to those without SOT. CONCLUSIONS: CAZ-AVI therapy was associated with better clinical outcomes in CRKP infections in both the general population and SOT recipients. Considering the limitations of the present study, well-conducted RCTs are still warranted to confirm these findings.


Subject(s)
Anti-Bacterial Agents , Azabicyclo Compounds , Ceftazidime , Drug Combinations , Klebsiella Infections , Klebsiella pneumoniae , Organ Transplantation , Humans , Ceftazidime/therapeutic use , Azabicyclo Compounds/therapeutic use , Male , Female , Retrospective Studies , Middle Aged , Klebsiella pneumoniae/drug effects , Klebsiella Infections/drug therapy , Klebsiella Infections/mortality , Klebsiella Infections/microbiology , Anti-Bacterial Agents/therapeutic use , Aged , Organ Transplantation/adverse effects , Carbapenem-Resistant Enterobacteriaceae/drug effects , Transplant Recipients , Adult , Carbapenems/therapeutic use , Treatment Outcome , Microbial Sensitivity Tests
3.
Front Aging Neurosci ; 16: 1349196, 2024.
Article in English | MEDLINE | ID: mdl-38419646

ABSTRACT

Background: Olfactory testing is emerging as a potentially effective screening method for identifying mild cognitive impairment in the elderly population. Objective: Olfactory impairment is comorbid with mild cognitive impairment (MCI) in older adults but is not well-documented in subdomains of either olfactory or subtypes of cognitive impairments in older adults. This meta-analysis was aimed at synthesizing the differentiated relationships with updated studies. Methods: A systematic search was conducted in seven databases from their availability to April 2023. A total of 38 publications were included, including 3,828 MCI patients and 8,160 healthy older adults. Two investigators independently performed the literature review, quality assessment, and data extraction. The meta-analyses were conducted with Stata to estimate the average effects and causes of the heterogeneity. Results: Compared to normal adults, MCI patients had severe impairments in olfactory function and severe deficits in specific domains of odor identification and discrimination. Olfactory impairment was more severe in patients with amnestic mild cognitive impairment than in patients with non-amnestic MCI. Diverse test instruments of olfactory function caused large heterogeneity in effect sizes. Conclusion: Valid olfactory tests can be complementary tools for accurate screening of MCI in older adults.

4.
Ren Fail ; 45(2): 2285873, 2023.
Article in English | MEDLINE | ID: mdl-38044852

ABSTRACT

OBJECTIVE: Peritoneal dialysis-related peritonitis (PDRP) presents a significant challenge for nephrologists. Continuous intraperitoneal cefazolin and ceftazidime are recommended for the treatment of peritonitis. However, some pharmacokinetic studies have shown that doses of 15-20 mg/kg/d may not achieve sufficient therapeutic levels. In this study, we investigated the pharmacokinetics of ceftazidime and cefazolin in patients with continuous ambulatory peritoneal dialysis-related peritonitis and compared the pharmacokinetic characteristics between traditional and modified treatment groups. METHODS: From February 2017 to December 2019, 42 PDRP patients (17 males, 25 females; mean age: 50.7 ± 12.1 years; mean body weight: 60.9 ± 11.8 kg) were recruited for the study, all participants were anuric. Twenty patients were enrolled in the traditional group and treated with cefazolin (1.0 g) and ceftazidime (1.0 g) via intraperitoneal administration once daily for 14 days. Twenty-two patients were enrolled in the modified group and received the same dose of antibiotics twice daily for the initial five days, followed by once daily for the subsequent nine days. Serum and dialysate samples were collected after days 1, 2, 3, 5, 7, 10, and 14 and analyzed via liquid chromatography-mass spectrometry. RESULTS: In the traditional group, the highest and lowest serum concentrations of ceftazidime were 35.9 and 21.7 µg/mL, respectively. The highest concentration of cefazolin was 54.6 µg/mL on day 5 and the lowest concentration was 30.4 µg/mL on day 1. In the modified group, the highest and lowest serum concentrations of ceftazidime were 102.2 and 54.8 µg/mL, respectively. The highest concentration of cefazolin was 141.7 µg/mL and the lowest concentration was 79.8 µg/mL. All antibiotic concentrations were above the minimum inhibitory concentration (MIC) level (8 µg/mL of ceftazidime and 2 µg/mL of cefazolin) throughout the treatment period. However, on day 1, the concentration of ceftazidime in the third bag of dialysate effluent from the traditional group fell below the MIC level. Despite remaining above the MIC, cefazolin concentration was consistently lower in the third bag of dialysate effluent from the traditional group throughout the treatment period. CONCLUSIONS: Intraperitoneal administration of cefazolin and ceftazidime at a dose of 1 g twice daily for 5 days and then once daily for the rest of the treatment period ensured adequate therapeutic levels of antibiotics for treating anuric PDRP patients.


Subject(s)
Anuria , Peritoneal Dialysis, Continuous Ambulatory , Peritonitis , Male , Female , Humans , Adult , Middle Aged , Cefazolin , Ceftazidime/pharmacokinetics , Ceftazidime/therapeutic use , Peritoneal Dialysis, Continuous Ambulatory/adverse effects , Peritoneal Dialysis, Continuous Ambulatory/methods , Prospective Studies , Anti-Bacterial Agents/therapeutic use , Peritonitis/drug therapy , Peritonitis/etiology , Dialysis Solutions , Anuria/etiology
5.
Crit Care ; 27(1): 248, 2023 06 23.
Article in English | MEDLINE | ID: mdl-37353839

ABSTRACT

PURPOSE: The significance of detecting human herpesvirus 7 (HHV-7) in the lower respiratory tract of patients with severe pneumonia is unclear. This study aims to evaluate the clinical characteristics and prognosis of detecting HHV-7 in the lower respiratory tract of patients with severe pneumonia. METHODS: Patients with severe pneumonia requiring invasive mechanical ventilation and underwent commercial metagenomic next-generation sequencing (mNGS) testing of bronchoalveolar lavage fluid from January 2019 to March 2023 were enrolled in 12 medical centers. Clinical data of patients were collected retrospectively, and propensity score matching was used for subgroup analysis and mortality assessment. RESULTS: In a total number of 721 patients, 45 cases (6.24%) were identified with HHV-7 positive in lower respiratory tract. HHV-7 positive patients were younger (59.2 vs 64.4, p = 0.032) and had a higher rate of co-detection with Cytomegalovirus (42.2% vs 20.7%, p = 0.001) and Epstein-Barr virus (35.6% vs 18.2%, p = 0.008). After propensity score matching for gender, age, SOFA score at ICU admission, and days from ICU admission to mNGS assay, there was no statistically significant difference in the 28-day mortality rate between HHV-7 positive and negative patients (46.2% vs 36.0%, p = 0.395). Multivariate Cox regression analysis adjusting for gender, age, and SOFA score showed that HHV-7 positive was not an independent risk factor for 28-day mortality (HR 1.783, 95%CI 0.936-3.400, p = 0.079). CONCLUSION: HHV-7 was detected in the lungs of 6.24% of patients with severe pneumonia. The presence of HHV-7 in patients with severe pneumonia requiring invasive mechanical ventilation is associated with a younger age and co-detected of Cytomegalovirus and Epstein-Barr virus. While HHV-7 positivity was not found to be an independent risk factor for mortality in this cohort, this result may have been influenced by the relatively small sample size of the study.


Subject(s)
Epstein-Barr Virus Infections , Herpesvirus 7, Human , Pneumonia , Humans , Retrospective Studies , Incidence , Herpesvirus 4, Human , Pneumonia/epidemiology , Lung , Cytomegalovirus
7.
Front Immunol ; 14: 1099468, 2023.
Article in English | MEDLINE | ID: mdl-36825017

ABSTRACT

Immunosuppressed patients can contract parvovirus B19, and some may experience hemophagocytic lymphohistiocytosis (HLH). Herein, we describe the first report of hemophagocytic lymphohistiocytosis in a heart-lung transplant patient with concomitant parvovirus B19 infection. The patient was treated with intravenous immune globulin (IVIG) and the features of HLH were remission. This instance emphasizes the significance of parvovirus B19 monitoring in transplant patients with anemia; if HLH complicates the situation, IVIG may be an adequate remedy. Finally, a summary of the development in diagnosing and managing parvovirus B19 infection complicated by HLH is provided.


Subject(s)
Erythema Infectiosum , Heart-Lung Transplantation , Lymphohistiocytosis, Hemophagocytic , Parvoviridae Infections , Parvovirus B19, Human , Humans , Lymphohistiocytosis, Hemophagocytic/diagnosis , Lymphohistiocytosis, Hemophagocytic/drug therapy , Erythema Infectiosum/complications , Immunoglobulins, Intravenous/therapeutic use , Heart-Lung Transplantation/adverse effects , Parvoviridae Infections/complications , Parvoviridae Infections/diagnosis
8.
J Med Virol ; 95(1): e28337, 2023 01.
Article in English | MEDLINE | ID: mdl-36418241

ABSTRACT

Viral reactivation is widespread in patients with severe pneumonia, yet the landscape of viral reactivation in the lungs is not well-known. This study aims to assess the landscape and clinical features of viral reactivation in the early onset of severe pneumonia in ICU patients. The clinical data from 97 patients were collected retrospectively from the intensive care units of five teaching hospitals between June 2018 and July 2021. Metagenomic next-generation sequencing (mNGS) of the bronchoalveolar lavage fluid (BALF) was performed at the onset of severe pneumonia. Cytomegalovirus (CMV), herpes simplex virus-1 (HSV-1), and Epstein-Barr virus (EBV) were the most common reactivated viruses in the lower respiratory tract of patients with severe pneumonia. After adjusting for the risk of confounding and competition of age, sex, sequential organ failure assessment, acute physiology chronic health assessment II and immunosuppression status, viral reactivation resulted in an overall 2.052-fold increase in 28-day all-cause mortality (95% CI: 1.004-4.194). This study showed that CMV, HSV-1, and EBV were the most common reactivated viruses in the lungs of patients with severe pneumonia. The existence of viral reactivations was associated with an increased risk of mortality. The simultaneous reactivation of multiple viruses needs to be considered in the design of clinical trials.


Subject(s)
Cytomegalovirus Infections , Epstein-Barr Virus Infections , Herpesvirus 1, Human , Pneumonia, Viral , Pneumonia , Humans , Retrospective Studies , Herpesvirus 4, Human/physiology , Cytomegalovirus/physiology , Lung
9.
Infect Drug Resist ; 15: 6755-6761, 2022.
Article in English | MEDLINE | ID: mdl-36447788

ABSTRACT

Hemorrhagic fever with renal syndrome (HFRS), caused by hanta viruses (HTNV), can be complicated by severe complications. Seventeen percent of the HFRS patients with abdominal pain had acute pancreatitis (AP). The reported prevalence of AP among HFRS patients has a conspicuous high mortality rate. Of note, acute capillary cholangitis (ACC) among HFRS patients presenting with abdominal pain appears extremely rare, particularly independent of HFRS patients complicated with AP. The main pathophysiological mechanism of HFRS complicated with AP and ACC may be that it preferentially damages the microvascular and induces plasma leakage. To date, the management of severe HFRS cases is mainly based on supportive treatment, including extracorporeal blood purification and mechanical ventilation. Here, we describe an exceptionally rare case of a 34-year man who developed HFRS with AP and ACC while improving from HTNV infection via antiviral and supportive treatment.

10.
Clin Rheumatol ; 41(11): 3383-3389, 2022 Nov.
Article in English | MEDLINE | ID: mdl-35882716

ABSTRACT

OBJECTIVES: To identify biomarkers that reflect disease activity scores and to investigate the role of macrophage-associated chemokines in initial axial spondyloarthritis (axSpA). METHOD: Patients with axSpA were enrolled. The SpondyloArthritis Research Consortium of Canada (SPARCC) method was used to score bone marrow oedema (BMO) in the inflammatory lesions on magnetic resonance imaging (MRI). Radiographic assessment of the spine was performed using the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS). Clinical variables, including inflammatory markers, serum CC chemokine ligand 2 (CCL2), CCL3, CCL7, CCL8 and C-X3-C motif ligand 1 (CX3CL1), were measured. Correlation analysis between serum levels of these macrophage-associated chemokines and clinical data was performed. RESULTS: There were no significant differences between the axSpA group and the healthy control group in terms of serum levels of CCL2, CCL3 or CCL8. Compared to the healthy control group, the serum levels of CCL7 and CX3CL1 were significantly higher in ankylosing spondylitis (AS) (p = 0.045, p = 0.017, respectively). In the AS subgroup, the serum level of CX3CL1 had a positive correlation with SPARCC scores. CONCLUSIONS: In AS, serum CCL7 and CX3CL1 levels are elevated. The serum level of CX3CL1 is associated with MRI-determined oedema in AS. CX3CL1 may be useful as a biomarker to predict active inflammation in the sacroiliac joint (SIJ) in AS. Key Points • Serum levels of CX3CL1 are associated with MRI-determined oedema in AS. • CX3CL1 may be a useful biomarker to predict active inflammation in the sacroiliac joint in AS.


Subject(s)
Axial Spondyloarthritis , Spondylarthritis , Spondylitis, Ankylosing , Biomarkers , Chemokines , Chemokines, CC , Edema/diagnostic imaging , Edema/pathology , Humans , Inflammation/pathology , Ligands , Macrophages , Magnetic Resonance Imaging/methods , Sacroiliac Joint/diagnostic imaging , Sacroiliac Joint/pathology , Severity of Illness Index , Spondylarthritis/complications , Spondylitis, Ankylosing/complications
11.
Front Immunol ; 12: 618830, 2021.
Article in English | MEDLINE | ID: mdl-33717113

ABSTRACT

Encephalitis caused by Epstein-Barr virus infection is uncommon, but most patients have a good outcome after symptomatic treatment. The infiltration of mononuclear cells in blood vessels and necrosis resulting from the immune response to Epstein-Barr virus infection in a very small number of patients seem to be the main cause of death. We describe a fatal case of Epstein-Barr virus encephalitis diagnosed by next-generation sequencing in an immune-competent adult but progressed to brainstem hemorrhage.


Subject(s)
Brain Stem/pathology , Cerebral Hemorrhage/etiology , Encephalitis, Viral/complications , Encephalitis, Viral/etiology , Epstein-Barr Virus Infections/complications , Epstein-Barr Virus Infections/etiology , Herpesvirus 4, Human , Biomarkers , Cerebral Hemorrhage/diagnosis , Encephalitis, Viral/diagnosis , Epstein-Barr Virus Infections/diagnosis , Fatal Outcome , Humans , Male , Middle Aged , Symptom Assessment , Tomography, X-Ray Computed
12.
Front Immunol ; 12: 768065, 2021.
Article in English | MEDLINE | ID: mdl-35069540

ABSTRACT

Balamuthia mandrillaris is one cause of a rare and severe brain infection called granulomatous amoebic encephalitis (GAE), which has a mortality rate of >90%. Diagnosis of Balamuthia GAE is difficult because symptoms are non-specific. Here, we report a case of Balamuthia amoebic encephalomyelitis (encephalitis and myelitis) in a woman with breast cancer. She sustained trauma near a garbage dump 2 years ago and subsequently developed a skin lesion with a Mycobacterium abscessus infection. She experienced dizziness, lethargy, nausea and vomiting, inability to walk, and deterioration of consciousness. Next-generation sequencing of cerebrospinal fluid (CSF) samples revealed B. mandrillaris, and MRI of both brain and spinal cord showed abnormal signals. T-cell receptor (TCR) sequencing of the CSF identified the Top1 TCR. A combination of amphotericin B, flucytosine, fluconazole, sulfamethoxazole, trimethoprim, clarithromycin, pentamidine, and miltefosine was administrated, but she deteriorated gradually and died on day 27 post-admission.


Subject(s)
Amebiasis , Breast Neoplasms , Encephalomyelitis , Adult , Amebiasis/drug therapy , Amebiasis/genetics , Amebiasis/immunology , Balamuthia mandrillaris/genetics , Balamuthia mandrillaris/immunology , Breast Neoplasms/drug therapy , Breast Neoplasms/genetics , Breast Neoplasms/immunology , Breast Neoplasms/parasitology , Encephalomyelitis/drug therapy , Encephalomyelitis/genetics , Encephalomyelitis/immunology , Encephalomyelitis/parasitology , Fatal Outcome , Female , High-Throughput Nucleotide Sequencing , Humans , Magnetic Resonance Imaging
13.
Front Immunol ; 12: 810677, 2021.
Article in English | MEDLINE | ID: mdl-35095902

ABSTRACT

Hemophagocytic lymphocytosis (HLH) is a rare disease caused by inborn errors of immunity (IEI), secondary to infection, lymphoma or autoimmune disorders, but we often overlook the fact that HLH can be secondary to inborn errors of metabolism (IEM). Here, we describe a patient who was diagnosed with glutaric aciduria type IIC complicated by features suggestive of possible HLH. The diagnosis of glutaric aciduria type IIC, a IEM, was confirmed by whole exome sequencing. The patient was treated with coenzyme Q10 and riboflavin which effectively improved her liver function. During treatment, the patient developed severe anemia and thrombocytopenia. Persistent fever, splenomegaly, cytopenias, increased ferritin, hypertriglyceridemia, hypofibrinogenemia, and hemophagocytosis in the bone marrow pointed to the diagnosis of HLH; however, the patient eventually died of gastrointestinal bleeding. After other potential causes were ruled out, the patient was diagnosed with glutaric aciduria type IIC complicated by features suggestive of possible HLH. When cytopenias occurs in IEM patients, HLH is a possible complication that cannot be ignored. This case suggests a possible relationship between IEM and risk for immune dysregulation.


Subject(s)
Lymphohistiocytosis, Hemophagocytic/complications , Lymphohistiocytosis, Hemophagocytic/diagnosis , Multiple Acyl Coenzyme A Dehydrogenase Deficiency/complications , Multiple Acyl Coenzyme A Dehydrogenase Deficiency/diagnosis , Adult , Biomarkers , Disease Susceptibility , Electron-Transferring Flavoproteins/genetics , Erythrocyte Indices , Female , Genetic Predisposition to Disease , Humans , Iron-Sulfur Proteins/genetics , Lymphohistiocytosis, Hemophagocytic/etiology , Magnetic Resonance Imaging , Oxidoreductases Acting on CH-NH Group Donors/genetics , Phenotype , Tomography, X-Ray Computed
14.
Front Microbiol ; 12: 833054, 2021.
Article in English | MEDLINE | ID: mdl-35222317

ABSTRACT

OBJECT: To reveal convergent IGH signatures and the association with severity of coronavirus disease 2019 (COVID-19) patients. METHOD: A total of 25 COVID-19 inpatients were classified into three clinical conditions: mild, severe, and critical. We analyzed convergent IGH signatures by ImmuHub® B-cell receptor (BCR) profiling system. RESULTS: IGH singleton frequency in patients is significantly lower than that of healthy donors (HDs). The clonality index of IGH in patients is significantly higher than that in HDs. Nevertheless, no significant difference was observed among the three groups. The difference in IGH clonality (top five clones) between post- and pretreatment was significant in the improvement and deterioration groups. Three common public motifs were shared by all COVID-19 patients: ARDYGG, RWYFDY, and YYYYGMDV. CONCLUSION: B cells could recognize severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and produce clonal expansion. Patients who had better outcomes after treatment had higher IGH clonality. Three common public motifs-ARDYGG, RWYFDY, and YYYYGMDV-might be used for vaccine development (ChiCTR2000029626).

15.
Clin Infect Dis ; 71(Suppl 4): S337-S362, 2020 12 23.
Article in English | MEDLINE | ID: mdl-33367581

ABSTRACT

The Chinese guidelines for IAI presented here were developed by a panel that included experts from the fields of surgery, critical care, microbiology, infection control, pharmacology, and evidence-based medicine. All questions were structured in population, intervention, comparison, and outcomes format, and evidence profiles were generated. Recommendations were generated following the principles of the Grading of Recommendations Assessment, Development, and Evaluation system or Best Practice Statement (BPS), when applicable. The final guidelines include 45 graded recommendations and 17 BPSs, including the classification of disease severity, diagnosis, source control, antimicrobial therapy, microbiologic evaluation, nutritional therapy, other supportive therapies, diagnosis and management of specific IAIs, and recognition and management of source control failure. Recommendations on fluid resuscitation and organ support therapy could not be formulated and thus were not included. Accordingly, additional high-quality clinical studies should be performed in the future to address the clinicians' concerns.


Subject(s)
Fistula , Intraabdominal Infections , Surgeons , China , Critical Care , Humans , Intraabdominal Infections/diagnosis , Intraabdominal Infections/drug therapy
16.
Front Immunol ; 11: 569082, 2020.
Article in English | MEDLINE | ID: mdl-33117355

ABSTRACT

Macrophage-stimulating protein (MSP), a soluble protein mainly synthesized by the liver, is the only known ligand for recepteur d'origine nantais (RON), which is a member of the MET proto-oncogene family. Recent studies show that the MSP-RON signaling pathway not only was important in tumor behavior but also participates in the occurrence or development of many immune system diseases. Activation of RON in macrophages results in the inhibition of nitric oxide synthesis as well as lipopolysaccharide (LPS)-induced inflammatory response. MSP-RON is also associated with chronic inflammatory responses, especially chronic liver inflammation, and might serve as a novel regulator of inflammation, which may affect the metabolism in the body. Another study provided evidence of the relationship between MSP-RON and autoimmune diseases, suggesting a potential role for MSP-RON in the development of drugs for autoimmune diseases. Moreover, MSP-RON plays an important role in maintaining the stability of the tissue microenvironment and contributes to immune escape in the tumor immune microenvironment. Here, we summarize the role of MSP-RON in immunity, based on recent findings, and lay the foundation for further research.


Subject(s)
Hepatocyte Growth Factor/metabolism , Immunity, Innate , Inflammation/etiology , Inflammation/metabolism , Proto-Oncogene Proteins/metabolism , Receptor Protein-Tyrosine Kinases/metabolism , Signal Transduction , Acute Disease , Animals , Biomarkers , Cellular Microenvironment/genetics , Cellular Microenvironment/immunology , Chronic Disease , Disease Susceptibility , Humans , Immune System/immunology , Immune System/metabolism , Macrophages/immunology , Macrophages/metabolism , Protein Binding , Proto-Oncogene Mas
17.
Eur J Clin Pharmacol ; 76(7): 913-922, 2020 Jul.
Article in English | MEDLINE | ID: mdl-32355990

ABSTRACT

PURPOSE: To analyze the clinical features and risk factors of tigecycline-associated hypofibrinogenaemia and study whether cefoperazone/sulbactam combined with tigecycline aggravates coagulopathy or hypofibrinogenaemia. METHODS: A retrospective case-control study of patients with severe infection who were treated with tigecycline was conducted. Patients were assigned to the hypofibrinogenaemia group (< 2.0 g/L) and normal fibrinogen (normal) group (≥ 2.0 g/L) to assess the clinical features of patients with tigecycline-associated hypofibrinogenaemia. The traits of patients treated with cefoperazone/sulbactam in the hypofibrinogenaemia group were also analyzed. RESULTS: In total, 127 patients were enrolled in the study, including 71 patients with hypofibrinogenaemia and 56 patients with normal fibrinogen levels. Hypofibrinogenaemia developed at a median of 6 (4-8) days after tigecycline treatment, and the fibrinogen level returned to normal at a median of 3 (3-5) days after tigecycline discontinuation. In the multivariate analysis, intra-abdominal infection (p = 0.005), fibrinogen level at tigecycline initiation (p < 0.001), maintenance dose (p = 0.039), and treatment duration (p = 0.002) were found to be related to hypofibrinogenaemia. Treatment with cefoperazone/sulbactam was not associated with hypofibrinogenaemia (p = 0.681), but patients treated with cefoperazone/sulbactam had a higher incidence of coagulopathy (p = 0.009) and needed more blood products (p = 0.003) than those treated without cefoperazone/sulbactam. CONCLUSION: Tigecycline-associated hypofibrinogenaemia often developed on the 6th (4th-8th) day of tigecycline use and was associated with intra-abdominal infection, fibrinogen level at tigecycline initiation, maintenance dose, and treatment duration of tigecycline but not cefoperazone/sulbactam.


Subject(s)
Afibrinogenemia/chemically induced , Anti-Bacterial Agents/adverse effects , Tigecycline/adverse effects , Adult , Afibrinogenemia/blood , Afibrinogenemia/epidemiology , Aged , Aged, 80 and over , Bacterial Infections/blood , Bacterial Infections/drug therapy , Bacterial Infections/epidemiology , Blood Coagulation Tests , Case-Control Studies , Cefoperazone/therapeutic use , Critical Illness , Female , Humans , Male , Middle Aged , Retrospective Studies , Risk Factors , Sulbactam/therapeutic use
18.
J Zhejiang Univ Sci B ; 21(5): 378-387, 2020 May.
Article in English | MEDLINE | ID: mdl-32425003

ABSTRACT

OBJECTIVE: This study summarizes and compares clinical and laboratory characteristics of 34 patients admitted to the intensive care unit (ICU) for complications from coronavirus disease 2019 (COVID-19) at the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China from Jan. 22 to Mar. 5, 2020. METHODS: A total of 34 patients were divided into two groups, including those who required noninvasive ventilation (NIV) and invasive mechanical ventilation (IMV) with additional extracorporeal membrane oxygenation (ECMO) in 11 patients. Clinical features of COVID-19 patients were described and the parameters of clinical characteristics between the two groups were compared. RESULTS: The rates of the acute cardiac and kidney complications were higher in IMV cases than those in NIV cases. Most patients had lymphocytopenia on admission, with lymphocyte levels dropping progressively on the following days, and the more severe lymphopenia developed in the IMV group. In both groups, T lymphocyte counts were below typical lower limit norms compared to B lymphocytes. On admission, both groups had higher than expected amounts of plasma interleukin-6 (IL-6), which over time declined more in NIV patients. The prothrombin time was increased and the levels of platelet, hemoglobin, blood urea nitrogen (BUN), D-dimer, lactate dehydrogenase (LDH), and IL-6 were higher in IMV cases compared with NIV cases during hospitalization. CONCLUSIONS: Data showed that the rates of complications, dynamics of lymphocytopenia, and changes in levels of platelet, hemoglobin, BUN, D-dimer, LDH and IL-6, and prothrombin time in these ICU patients were significantly different between IMV and NIV cases.


Subject(s)
Coronavirus Infections/complications , Coronavirus Infections/therapy , Noninvasive Ventilation , Pneumonia, Viral/complications , Pneumonia, Viral/therapy , Positive-Pressure Respiration , Acute Kidney Injury/virology , Aged , Aged, 80 and over , Betacoronavirus , Blood Urea Nitrogen , COVID-19 , China , Extracorporeal Membrane Oxygenation , Female , Fibrin Fibrinogen Degradation Products/analysis , Heart Diseases/virology , Hemoglobins/analysis , Hospitalization , Humans , Intensive Care Units , Interleukin-6/blood , L-Lactate Dehydrogenase/blood , Lymphopenia/virology , Male , Middle Aged , Pandemics , Prothrombin Time , Retrospective Studies , SARS-CoV-2
19.
Front Cell Infect Microbiol ; 10: 606340, 2020.
Article in English | MEDLINE | ID: mdl-33537243

ABSTRACT

The macrophage stimulating protein (MSP)-Recepteur d'origine nantais (RON) signaling pathway regulates macrophage function. Here, we verified RON receptor expression in bone marrow-derived dendritic cells (BMDCs) by real time-PCR, Western blot, and flow cytometry. Flow cytometry was used to detect the changes in MHC II and CD86 expression following the inhibition of RON in BMDCs and splenic dendritic cells (DCs). Immunoprecipitation and Western blot were used to detect the level of MHC II and CD86 ubiquitination. An enzyme-linked immunosorbent assay was used to detect cytokine release, and a mixed lymphocyte reaction was performed to evaluate DC maturity. The results show that the inhibition of RON leads to an increase in March-1 transcription, which intensifies the ubiquitination of MHC II and CD86 and ultimately leads to a decreased level of these two molecules. The mixed lymphocyte reaction provided evidence that RON inhibition decreased the ability of DCs to promote the proliferation of T cells. The MSP-RON signaling pathway may play an important role in lipopolysaccharide (LPS)-stimulated DC maturation through March-I and may protect DC differentiation following LPS stimulation.


Subject(s)
Lipopolysaccharides , Signal Transduction , Cell Differentiation , Dendritic Cells
20.
Biomed Pharmacother ; 118: 109175, 2019 Oct.
Article in English | MEDLINE | ID: mdl-31351423

ABSTRACT

Increasing research indicates that hyperglycemia plays a crucial role in the progression of diabetic nephropathy (DN); however, effective treatment for preventing or slowing DN progression are seriously lacking. Although salidroside (SAL) has been demonstrated to have a positive anti-diabetic effect, the cellular mechanisms remain unclear. FG-4592, a novel prolyl hydroxylase inhibitor, was used to regulate HIF-1α and HIF-2α expression. The present study aimed to explore the underlying mechanisms of SAL and FG-4592 on high glucose (HG)-induced rat glomerular endothelial cells (rGECs) injury. HG-cultured rGECs were used to induce a diabetic environment. An MTT assay, RT-qPCR, Western blot, flow cytometry, and immunofluorescent staining were performed to investigate the effects of SAL on HG-induced rGECs injury. FG-4592 and SAL protected rGECs against HG-induced injury by increasing cellular viability and reducing the cell apoptosis rate. SAL and FG-4592 downregulated PHD-2 expression and upregulated HIF-1α and HIF-2α expression. In conclusion, our findings suggest that SAL and FG-4592 ameliorate HG-induced rGEC injury by upregulating HIF expression, indicating that SAL and FG-4592 might be favorable for further DN-treatment.


Subject(s)
Basic Helix-Loop-Helix Transcription Factors/biosynthesis , Endothelial Cells/drug effects , Glucose/toxicity , Glucosides/pharmacology , Glycine/analogs & derivatives , Hypoxia-Inducible Factor 1, alpha Subunit/biosynthesis , Isoquinolines/pharmacology , Kidney Glomerulus/drug effects , Phenols/pharmacology , Animals , Apoptosis/drug effects , Cell Survival/drug effects , Cells, Cultured , Diabetic Nephropathies/metabolism , Diabetic Nephropathies/pathology , Endothelial Cells/metabolism , Endothelial Cells/pathology , Glucosides/administration & dosage , Glycine/administration & dosage , Glycine/pharmacology , Isoquinolines/administration & dosage , Kidney Glomerulus/metabolism , Kidney Glomerulus/pathology , Phenols/administration & dosage , Protein Stability , Rats , Up-Regulation
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