Mechanistic Study of Glycyrrhizic Acid Improving Alcoholic Fatty Liver Disease by Modulating the SHP1/SYK Signaling Pathway in Macrophages.

Objective: To investigate glycyrrhizin's effects and molecular mechanisms on the progression of alcoholic fatty liver. Methods: An alcoholic fatty liver model was established, followed by the administration of glycyrrhizin ammonium (20 mg/kg). Liver tissue pathological changes were observed using oil red O staining, and pyroptotic bodies were observed using transmission electron microscopy. Western blot was used to detect the expression of related proteins. To establish a model of alcoholic fatty liver cells to explore the molecular mechanism of glycolic acid in this disease. Results: Glycyrrhizin ammonium reduced the area of oil red staining in liver tissue and the number of pyroptotic bodies decreased the relative protein expression of NOX2, NOX3, p-SYK, STING, p-PDE4B, NLRP3, IL-1ß, GSDMD, Caspase-1, and Caspase-4, and increased the relative protein expression of p-SHP1 and Nrf2. Conclusion: Glycyrrhizin ameliorates the progression of alcoholic fatty liver by modulating the SHP1/SYK signaling pathway in macrophages, thereby inhibiting hepatic lipid peroxidation and pyroptosis.

Effect of Infusion Set Replacement Intervals on Central Line-Associated Bloodstream Infection in the Intensive Care Unit: Study Protocol of the INSPIRATION Study.

INTRODUCTION: The replacement intervals for infusion sets may differ among healthcare institutions, which may have an impact on the occurrence of central line-associated bloodstream infections (CLABSI). Nevertheless, there exists a limited amount of high-quality evidence available to assist clinicians in determining the most suitable replacement intervals for infusion sets. Therefore, the objective of this trial is to compare the efficacy of 24-h and 96-h replacement intervals for infusion sets on CLABSI among critically ill adults who have central venous access devices. METHODS: This is a multicenter, parallel-group randomized controlled trial that will investigate the effect of infusion set replacement intervals on CLABSI in adult patients admitted to intensive care units (ICUs). The study will enroll 1240 participants who meet the inclusion criteria, which includes being 18 years or older, expected to stay in the ICU for longer than 96 h, and in need of central venous access. Participants will be randomly assigned to either a control group receiving a 96-h replacement interval or a treatment group receiving a 24-h replacement interval. PLANNED OUTCOME: The primary outcome of this trial is the rate of CLABSI within 28 days after randomization. CONCLUSION: This is the first randomized controlled trial to investigate the effects of infusion set replacement at 24-h and 96-h intervals on CLABSI in ICU patients. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT05359601.

Sepsis and multi-organ failure due to genital herpes in a healthy person.

Herpes simplex virus type 2 (HSV-2) is highly prevalent in several regions of the world and is the main pathogen causing genital herpes, which is transmitted almost exclusively through sexual contact. Systemically disseminated infections caused by HSV-2 are rare and most often seen in newborns, pregnant women, or immunocompromised populations. The virus can invade multiple organs and cause damage. In this paper, we present an extremely rare case of an immunocompetent 36-year-old male who came to our hospital with a high fever with abdominal pain and died of sepsis and multiple organ dysfunction syndrome within a short period. After the exclusion of common pathogens such as bacterial and fungal infections during hospitalization, metagenomic next generation sequencing of the patient's peripheral blood and ascites gave us the answer, and very high nucleic acid sequence counts of HSV-2 were detected in both his peripheral blood and ascites, confirming HSV-2 as the causative virus. In addition, this paper provides a brief review of the relevant literature.

A prospective study of nanopore-targeted sequencing in the diagnosis of central nervous system infections.

Central nervous system (CNS) infections are a leading cause of death in patients. Nanopore-targeted sequencing (NTS) has begun to be used for pathogenic microbial detection. This study aims to evaluate the ability of NTS in the detection of pathogens in cerebrospinal fluid (CSF) through a prospective study. Fifty CSF specimens collected from 50 patients with suspected CNS infections went through three methods including NTS, metagenomic next-generation sequencing (mNGS), and microbial culture in parallel. When there was an inconsistency between NTS results and the results of the mNGS, the 16S rDNA gene was amplified followed by Sanger sequencing to further verify pathogens detected by NTS. Among 50 CSF specimens, 76% were NTS-positive, which is lower than mNGS (94.0%), yet higher than microbial culture (16.0%). The overall validation rate, diagnostic accordance rate (DAR), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of NTS were 86.7%, 50.0%, 71.0%, 15.8%, 57.9%, and 25.0%, respectively. In the CSF total nucleated cell (TNC) number ≤10 cells/µL, DAR, specificity, and PPV were 20%, 11.1%, and 11.1%, whereas in that with CSF TNC number >10 cells/µL, DAR, sensitivity, specificity, PPV, and NPV were 57.5%, 70.0%, 20.0%, 72.4%, and 18.2%, respectively. Although NTS has a higher microbial detection rate than microbial culture, it should combine CSF TNC result to evaluate the value of NTS for the diagnosis of CNS infections. IMPORTANCE: This study aims to prospectively evaluate the ability of nanopore-targeted sequencing (NTS) in the detection of pathogens in cerebrospinal fluid (CSF). It was the first time combining mNGS and microbial culture to verify the NTS-positive results also using 16S rDNA amplification with Sanger sequencing. Although microbial culture was thought to be the gold standard for pathogens detection and diagnosis of infectious diseases, this study suggested that microbial culture of CSF is not the most appropriate way for diagnosing central nervous system (CNS) infection. NTS should be recommended to be used in CSF for diagnosing CNS infection. When evaluating the value of NTS for diagnosis of CNS infections, the results of CSF TNC should be combined, and NTS-positive result is observed to be more reliable in patients with CSF TNC level >10 cells/µL.

ADHD in narcolepsy: A closer look at prevalence and ties.

The reported prevalence of attention deficit hyperactivity disorder (ADHD) in narcolepsy varies considerably, while the associated factors remain inadequately established. A systematic search of studies published in PubMed, EMBASE, and the Cochrane Library was performed from inception to March 2023. Ten studies with 839 patients with narcolepsy were included in the study. Utilizing a random effects model, the pooled prevalence of ADHD in narcolepsy was 25% (95% CI, 14-38%). Notably, patients with narcolepsy type 2 showed a significantly higher prevalence of ADHD than that of narcolepsy type 1 (46% vs. 20%, p = 0.045). Furthermore, the rate of ADHD was notably elevated in narcolepsy compared with the healthy controls (odds ratio 9.59, 95% CI, 4.06-22.63, p < 0.001). Several factors such as excessive daytime sleepiness (EDS), fatigue, insomnia severity, and the quality of life were significantly associated with ADHD in narcolepsy (all ps < 0.05). These findings highlight the importance of monitoring and managing ADHD in narcolepsy, and provide a clue to help reducing ADHD by intervening in these associated factors.

The role of the immune response and inflammatory pathways in TNF-related apoptosis-inducing ligand (TRAIL) resistance in triple-negative breast cancer cells.

Triple-negative breast cancer (TNBC) is an aggressive form of breast cancer, and the majority of TNBC lacks targeted therapies. Previous studies have shown that TNBC cells are highly sensitive to TNF-related apoptosis-inducing ligand (TRAIL), making it a potentially viable treatment option for TNBC. However, the development of TRAIL resistance limits its potential for clinical use, and the underlying mechanisms are not fully understood. To better understand the mechanism of resistance to TRAIL, we performed RNA sequencing to identify the candidates that are responsible for resistance to TRAIL in two previously established TRAIL-resistant MDA231 and SUM159 cells. This approach led us to identify differentially expressed genes (DEGs) and pathways in TRAIL-resistant MDA231 and SUM159 cells compared to their TRAIL-sensitive counterparts. We showed that several DEGs and pathways were associated with inflammation in TRAIL-resistant cells, including IL-1α and IL6. By downregulating IL-1α and IL6 expression, we showed that TRAIL sensitivity can be significantly restored in TRAIL-resistant cells. Therefore, this study identifies a mechanism by which the inflammation pathway promotes TRAIL resistance, which could be targeted for enhancing TRAIL-based therapies in TNBC cells.

Aldolase A promotes cervical cancer cell radioresistance by regulating the glycolysis and DNA damage after irradiation.

Radioresistance is the major obstacle that affects the efficacy of radiotherapy which is an important treatment for cervical cancer. By analyzing the databases, we found that aldolase A (ALDOA), which is a key enzyme in metabolic reprogramming, has a higher expression in cervical cancer patients and is associated with poor prognosis. We detected the expression of ALDOA in the constructed cervical cancer radioresistance (RR) cells by repetitive irradiation and found that it was upregulated compared to the control cells. Functional assays were conducted and the results showed that the knockdown of ALDOA in cervical cancer RR cells inhibited the proliferation, migration, and clonogenic abilities by regulating the cell glycolysis. In addition, downregulation of ALDOA enhanced radiation-induced apoptosis and DNA damage by causing G2/M phase arrest and further promoted radiosensitivity of cervical cancer cells. The functions of ALDOA in regulating tumor radiosensitivity were also verified by the mouse tumor transplantation model in vivo. Therefore, our study provides new insights into the functions of ALDOA in regulating the efficacy of radiotherapy and indicates that ALDOA might be a promising target for enhancing radiosensitivity in treating cervical cancer patients.

Hypoxic tumor cell-derived small extracellular vesicle miR-152-3p promotes cervical cancer radioresistance through KLF15 protein.

BACKGROUND: Radiotherapy is widely used in treating cervical cancer patients, however, radioresistance unavoidably occurs and seriously affects the treatment effect. It is well known that hypoxia plays an important role in promoting radioresistance in tumor microenvironment, yet our understanding of the effect of small extracellular vesicles miRNA on cervical cancer radiosensitivity in hypoxic environment is still limited. METHODS: Small extracellular vesicles extracted from hypoxic and normoxic cultured cervical cancer cells were evaluated for their effects on radioresistance. miR-152-3p was found to be a potential effector in hypoxia-derived extracellular vesicles by searching the GEO database. Its downstream substrate was confirmed by double luciferase report, which was KLF15. The role of miR-152-3p and KLF15 in regulating cervical cancer radioresistance was detected by cell activity assays. The findings were confirmed in vivo by animal models. The expression of miR-152-3p was quantified by qRT-PCR and its prognostic significance was evaluated. RESULTS: Hypoxic environment promoted the secretion of small extracellular vesicles, and reduced the apoptosis and DNA damage caused by radiation, accompanied by increased expression of small extracellular vesicles miR-152-3p from hypoxic cervical cancer cells. Furthermore, small extracellular vesicles miR-152-3p promoted Hela xenograft growth and reduced the radiosensitivity vivo. Mechanism studies revealed that KLF15 protein was the downstream target of miR-152-3p in regulating radioresistance. CONCLUSION: Our findings suggest that small extracellular vesicles miR-152-3p affects the therapeutic effect of radiotherapy and holds potential as a biomarker or therapeutic target for cervical cancer prognosis and improving radiotherapy.

Treatment strategies for intrauterine adhesion: focus on the exosomes and hydrogels.

Intrauterine adhesion (IUA), also referred to as Asherman Syndrome (AS), results from uterine trauma in both pregnant and nonpregnant women. The IUA damages the endometrial bottom layer, causing partial or complete occlusion of the uterine cavity. This leads to irregular menstruation, infertility, or repeated abortions. Transcervical adhesion electroreception (TCRA) is frequently used to treat IUA, which greatly lowers the prevalence of adhesions and increases pregnancy rates. Although surgery aims to disentangle the adhesive tissue, it can exacerbate the development of IUA when the degree of adhesion is severer. Therefore, it is critical to develop innovative therapeutic approaches for the prevention of IUA. Endometrial fibrosis is the essence of IUA, and studies have found that the use of different types of mesenchymal stem cells (MSCs) can reduce the risk of endometrial fibrosis and increase the possibility of pregnancy. Recent research has suggested that exosomes derived from MSCs can overcome the limitations of MSCs, such as immunogenicity and tumorigenicity risks, thereby providing new directions for IUA treatment. Moreover, the hydrogel drug delivery system can significantly ameliorate the recurrence rate of adhesions and the intrauterine pregnancy rate of patients, and its potential mechanism in the treatment of IUA has also been studied. It has been shown that the combination of two or more therapeutic schemes has broader application prospects; therefore, this article reviews the pathophysiology of IUA and current treatment strategies, focusing on exosomes combined with hydrogels in the treatment of IUA. Although the use of exosomes and hydrogels has certain challenges in treating IUA, they still provide new promising directions in this field.

Sex differences in rapid eye movement sleep behavior disorder: A systematic review and meta-analysis.

Although rapid eye movement (REM) sleep behavior disorder (RBD) has been widely considered as a male-predominant parasomnia, the existing evidence for the sex difference in the risk of RBD in the general population was conflicting. The present study conducted a systematic review to explore the sex differences in the prevalence, comorbidities, clinical characteristics, and phenoconversion of RBD. One hundred thirty-five eligible studies were identified for the systematic review, and 133 were finally included in the meta-analysis. Males in the general population showed a trend for a higher risk of probable/possible RBD (pRBD), especially among the male older adults (aged ≥60). In the clinical populations, males showed a significantly higher risk of confirmed RBD, but not of pRBD. Among idiopathic RBD (iRBD) patients, males had a significantly earlier age onset of RBD compared with females. Male patients with Parkinson's disease (PD) had a higher risk of comorbid RBD. There was no significant sex difference in the risk of developing neurodegenerative diseases in iRBD patients. Large scale and prospective studies utilizing stringent diagnostic criteria for RBD are recommended to further verify the sex differences in RBD and to investigate the mechanism underlying the sex difference.

Analysis of Lung Microbiome in COVID-19 Patients during Time of Hospitalization.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is the pathogenic agent of the rapidly spreading pneumonia called coronavirus disease 2019 (COVID-19), primarily infects the respiratory and digestive tract. Several studies have indicated the alterations of the bacterial microbiome in the lower respiratory tract during viral infection. However, both bacterial and fungal microbiota in the lung of COVID-19 patients remained to be explored. METHODS: In this study, we conducted nanopore sequencing analyses of the lower respiratory tract samples from 38 COVID-19 patients and 26 non-COVID-19 pneumonia controls. Both bacterial and fungal microbiome diversities and microbiota abundances in the lung were compared. RESULTS: Our results revealed significant differences in lung microbiome between COVID-19 patients and non-COVID-19 controls, which were strongly associated with SARS-CoV-2 infection and clinical status. COVID-19 patients exhibited a notably higher abundance of opportunistic pathogens, particularly Acinetobacter baumannii and Candida spp. Furthermore, the potential pathogens enriched in COVID-19 patients were positively correlated with inflammation indicators. CONCLUSIONS: Our study highlights the differences in lung microbiome diversity and composition between COVID-19 patients and non-COVID-19 patients. This may contribute to predicting co-pathogens and selecting optimal treatments for respiratory infections caused by SARS-CoV-2.

The Role of TRAIL in Apoptosis and Immunosurveillance in Cancer.

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a member of the TNF superfamily that selectively induces apoptosis in tumor cells without harming normal cells, making it an attractive agent for cancer therapy. TRAIL induces apoptosis by binding to and activating its death receptors DR4 and DR5. Several TRAIL-based treatments have been developed, including recombinant forms of TRAIL and its death receptor agonist antibodies, but the efficacy of TRAIL-based therapies in clinical trials is modest. In addition to inducing cancer cell apoptosis, TRAIL is expressed in immune cells and plays a critical role in tumor surveillance. Emerging evidence indicates that the TRAIL pathway may interact with immune checkpoint proteins, including programmed death-ligand 1 (PD-L1), to modulate PD-L1-based tumor immunotherapies. Therefore, understanding the interaction between TRAIL and the immune checkpoint PD-L1 will lead to the development of new strategies to improve TRAIL- and PD-L1-based therapies. This review discusses recent findings on TRAIL-based therapy, resistance, and its involvement in tumor immunosurveillance.

Donor-Derived Transmission of Scedosporiosis in Kidney Transplant Recipients from a Systemic lupus erythematosus donor.

Donor-derived infection (DDI) associated with Scedosporium spp is extremely rare, and results in a very poor prognosis. The present study reports a probable DDI due to Scedosporium boydii (S. boydii) from a donor with neuropsychiatric systemic lupus erythematosus. Two recipients developed Scedosporiosis after kidney transplantation from the same donor. Recipient 1 died of central nervous system infection due to S. boydii based on the clinical presentations, and the positive metagenomic next-generation sequencing (mNGS) and culture results for the cerebrospinal fluid. The other recipient with urinary tract obstruction due to S. boydii, which was identified through the positive culture and mNGS results of the removed stents, was successfully treated by stent replacement and voriconazole administration. Undiagnosed disseminated donor infection and the transmission of S. boydii should be given attention, particularly when the donor and recipients have primary immunodeficiency disease. The screening of donors and recipients for S. boydii using mNGS may be helpful in guiding antifungal prophylaxis and treatment recipients, due to its higher sensitivity and shorter diagnostic time relative to other traditional techniques.

Population genomic analysis provides evidence of the past success and future potential of South China tiger captive conservation.

BACKGROUND: Among six extant tiger subspecies, the South China tiger (Panthera tigris amoyensis) once was widely distributed but is now the rarest one and extinct in the wild. All living South China tigers are descendants of only two male and four female wild-caught tigers and they survive solely in zoos after 60 years of effective conservation efforts. Inbreeding depression and hybridization with other tiger subspecies were believed to have occurred within the small, captive South China tiger population. It is therefore urgently needed to examine the genomic landscape of existing genetic variation among the South China tigers. RESULTS: In this study, we assembled a high-quality chromosome-level genome using long-read sequences and re-sequenced 29 high-depth genomes of the South China tigers. By combining and comparing our data with the other 40 genomes of six tiger subspecies, we identified two significantly differentiated genomic lineages among the South China tigers, which harbored some rare genetic variants introgressed from other tiger subspecies and thus maintained a moderate genetic diversity. We noticed that the South China tiger had higher FROH values for longer runs of homozygosity (ROH > 1 Mb), an indication of recent inbreeding/founder events. We also observed that the South China tiger had the least frequent homozygous genotypes of both high- and moderate-impact deleterious mutations, and lower mutation loads than both Amur and Sumatran tigers. Altogether, our analyses indicated an effective genetic purging of deleterious mutations in homozygous states from the South China tiger, following its population contraction with a controlled increase in inbreeding based on its pedigree records. CONCLUSIONS: The identification of two unique founder/genomic lineages coupled with active genetic purging of deleterious mutations in homozygous states and the genomic resources generated in our study pave the way for a genomics-informed conservation, following the real-time monitoring and rational exchange of reproductive South China tigers among zoos.

Early- and late-onset narcolepsy: possibly two distinct clinical phenotypes.

PURPOSE: To investigate the clinical characteristics and the risk factors associated with excessive daytime sleepiness (EDS) in patients with early- and late-onset narcolepsy. METHODS: Patients with narcolepsy were consecutively recruited. All patients were separated into early- and late-onset groups according to the onset age of disease ≤ 15 and > 15 years, respectively. Demographic, clinical, and sleep parameters were compared between the two groups. Linear regressions were performed to examine the risk factors of subjective and objective EDS in patients with early- and late-onset narcolepsy. RESULTS: A total of 101 patients with narcolepsy (median age at recruitment = 18.0 years) were classified into an early-onset group (67 patients with median age at onset = 12.0 years) and a late-onset group (34 patients with median age at onset = 28.5 years). Compared with early-onset group, late-onset group scored significantly higher on Epworth Sleepiness Scale (ESS), Ullanlinna Narcolepsy Scale (UNS), sleep paralysis, rapid eye movement (REM) sleep behavior disorder (RBD) questionnaire-Hong Kong (all P < 0.050). UNS-cataplexy and sleep paralysis had significantly positive associations with subjective EDS, and N1%, arousal index, and periodic limb movements index were positively associated with objective EDS in the early-onset group (all P < 0.050). However, these associations were not observed in late-onset narcolepsy. CONCLUSION: Late onset narcolepsy had more severe self-reported narcolepsy symptoms. REM sleep related symptoms and disrupted nighttime sleep were associated with EDS in early-onset narcolepsy. These findings suggest that early- and late-onset narcolepsy may represent two distinct phenotypes.

Characterization of fecal microbiota in cervical cancer patients associated with tumor stage and prognosis.

Cervical cancer (CC) is the fourth most frequent malignancy among women worldwide, and its prevention and treatment are evolving rapidly. The gut microbiota has been reported to play a crucial role both in the preservation of homeostasis and the development of cervical cancer. In this study, we collected fecal samples to investigate the microbial signatures in cervical cancer patients compared with healthy controls using 16S rRNA sequencing analysis and metagenomic next-generation sequencing (mNGS) testing. Our findings demonstrated a substantial difference in the gut microbiota composition of cervical cancer patients and healthy controls. The disease and stage were most significantly negatively correlated with Ruminococcus 2, which might be considered a potential clinically relevant biomarker. Functions of differential microbiomes were also analyzed, indicating significant differences in metabolisms and biosynthesis between the two groups. These findings demonstrate that patients with cervical cancer have certain species of gut microbiota that are exclusive to them and particular species have the potential to be used in the prognosis of cervical cancer.

Clinical phase I/II trial of SVF therapy for cartilage regeneration: A cellular therapy with novel 3D MRI imaging for evaluating chondral defect of knee osteoarthritis.

Background: The clinical applications of stromal vascular fraction (SVF) therapy for osteoarthritis (OA) have attracted academic and clinical attention. However, data of the effects of stromal vascular fraction therapy on regeneration of degenerated cartilage are limited in the literature. Meanwhile, there is a great need for a simple and non-invasive evaluation method to analyze the changes of joint cartilage qualitatively and quantitatively in clinical trials. This study entitled "stromal vascular fraction Therapy for Human Knee Osteoarthritis" was registered in ClinicalTrial.gov # NCT05019378. Materials and Methods: We designed and conducted a single center, open labeled clinical phase I/II study, and 6 osteoarthritis patients with both knee cartilage defect I-II were enrolled in this study. The two knees of each patient were randomly assigned to autologous stromal vascular fraction treatment group or non-treatment control group to evaluate the safety and therapeutic effect of stromal vascular fraction therapy for human knee osteoarthritis. We have also established a novel protocol to provide 3D MRI imaging for human knee cartilage enabling us to qualitatively and quantitatively evaluate cartilage degeneration and regeneration in this study. Results: The qualitative and quantitative evaluation of 3D Magnetic Resonance Imaging (MRI) imaging of knee cartilage demonstrated that the stromal vascular fraction therapy reduced the cartilage defects; and significant increase of cartilage value both in defect cartilage area and whole cartilage area of treated group and significant increase of thickness and area of both femoral and tibia cartilage in vertical sections of the stromal vascular fraction treated Group at 12 and 24 W post treatment in cartilage defect I-II osteoarthritis patients. Conclusion: This clinical phase I/II study indicated that stromal vascular fraction therapy is a safe clinical procedure and provided evidence that the stromal vascular fraction therapy significantly facilitated cartilage regeneration, opening the opportunity to a phase III trial investigating authentic efficacy of the procedure. This study is the first qualitative and quantitative evaluation of the efficacy of autologous stromal vascular fraction cellular therapy on cartilage regeneration. Through early and definite diagnosis of knee osteoarthritis patients, and providing safe and efficient therapy to facilitate cartilage regeneration, we will be able to control or reverse cartilage degeneration and completely change the epidemiology of osteoarthritis worldwide.

Regulation of programmed death ligand 1 (PD-L1) expression by TNF-related apoptosis-inducing ligand (TRAIL) in triple-negative breast cancer cells.

Triple-negative breast cancer (TNBC) is an aggressive form of breast cancer that lacks targeted therapies. Previous studies have shown that TNBC cells are highly sensitive to tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), making it a promising agent for treating TNBC. However, the development of TRAIL resistance limits its further clinical development, and the underlying mechanisms are not fully understood. In this study, we report the role of PD-L1 in TRAIL resistance. Specifically, we found that TRAIL treatment increases PD-L1 expression in TRAIL-sensitive cells and that basal PD-L1 expression is increased in acquired TRAIL-resistant cells. Mechanistically, we found that increased PD-L1 expression was accompanied by increased extracellular signal-regulated kinase (ERK) activation. Using both genetic and pharmacological approaches, we showed that knockdown of ERK by siRNA or inhibition of ERK activation by the mitogen-activated protein kinase kinase inhibitor U0126 decreased PD-L1 expression and increased TRAIL-induced cell death. Furthermore, we found that knockout or knockdown of PD-L1 enhances TRAIL-induced apoptosis, suggesting that PD-L1-mediated TRAIL resistance is independent of its ability to evade immune suppression. Therefore, this study identifies a noncanonical mechanism by which PD-L1 promotes TRAIL resistance, which can be potentially exploited for immune checkpoint therapy.

Distribution and drug resistance analysis of pathogenic bacteria in a hospital blood culture, 2018-2022 / 中国热带医学

@#Abstract: Objective　To analyze the distribution and drug resistance of pathogenic bacteria in blood culture specimens of patients with bloodstream infections before and after COVID-19 (2018-2019 and 2020-2021), and to provide scientific basis and reference for rational treatment and effective control of bloodstream infections in the post-epidemic period. Methods Blood culture specimens were collected from patients in Zhongnan Hospital of Wuhan University in the two years before and after the COVID-19 outbreak (2018-2021). The Automated Blood Culture Systems were used to perform blood culture on blood specimens sent for clinical inspection, and the Vitek MS automatic bacterial identification mass spectrometer was used for strain identification and the Vitek 2 automatic bacterial drug susceptibility analyzer was used for drug susceptibility testing and drug resistance analysis. Results　Blood culture specimens were performed on 28 736 patients with suspected bloodstream infection submitted for inspection from January 2018 to December 2019, and a total of 2 181 strains of pathogenic bacteria were detected after removing duplicate strains, with a positive rate of 7.69%, including 1 046 strains of Gram-negative bacteria, accounting for 47.96%. From January 2020 to December 2021, blood culture specimens from 26 083 patients with suspected bloodstream infection were submitted for inspection, and a total of 2 111 strains of pathogenic bacteria were detected after excluding duplicate strains, with a positive rate of 8.09%, including 1 000 strains of Gram-negative bacteria accounted for 47.37%. The drug resistance of Klebsiella pneumoniae was relatively serious, and the sensitivity rate to ertapenem, polymyxin B and tigecycline was more than 90%. The main non-fermentative bacteria Acinetobacter baumannii was more than 50% sensitive to piperacillin/tazobactam, amikacin and polymyxin B. The sensitivity rates of Pseudomonas aeruginosa to piperacillin/tazobactam, ceftazidime, cefepime, amikacin, gentamicin, tobramycin, ciprofloxacin, levofloxacin, piperacillin and meropenem were more than 50%. Conclusions　In the two years before and after COVID-19, there are many types of pathogenic bacteria in bloodstream infection, but the distribution do not differ significantly. The pathogens of bloodstream infection are mainly distributed in ICU, hepatobiliary research institute, and nephrology department. Among them, Gram-negative bacteria such as Escherichia coli, Klebsiella pneumoniae and Acinetobacter baumannii are the main ones, and different pathogens showed great differences in drug resistance.