Repurposing a human acetyl-CoA carboxylase inhibitor firsocostat to treat fungal candidiasis alone and in combination.

Opportunistic fungal infections, particularly caused by Candida albicans, remain a common cause of high morbidity and mortality in immunocompromised patients. The escalating prevalence of antifungal drug resistance necessitates the immediate exploration of alternative treatment strategies to combat these life-threatening fungal diseases. In this study, we investigated the antifungal efficacy of firsocostat, a human acetyl-CoA carboxylase (ACC) inhibitor, against C. albicans. Firsocostat alone displayed moderate antifungal activity, while combining it with voriconazole, itraconazole, or amphotericin B exhibited synergistic effects across almost all drug-sensitive and drug-resistant C. albicans strains tested. These observed synergies were further validated in two mouse models of oropharyngeal and systemic candidiasis, where the combination therapies demonstrated superior fungicidal effects compared to monotherapy. Moreover, firsocostat was shown to directly bind to C. albicans ACC and inhibit its enzymatic activity. Sequencing spontaneous firsocostat-resistant mutants revealed mutations mapping to C. albicans ACC, confirming that firsocostat has retained its target in C. albicans. Overall, our findings suggest that repurposing firsocostat, either alone or in combination with other antifungal agents, holds promising potential in the development of antifungal drugs and the treatment of candidiasis.

Paraffin-embedded Sample Test Promotes the Diagnosis of Tuberculous Pleurisy.

Context: Tuberculous pleurisy (TP) is the most common manifestation of extrapulmonary tuberculosis and the most frequent cause of pleural effusion (PE). Clinicians make a definitive diagnosis of TP based on the isolation of the mycobacterium tuberculosis (MTB) from PE or a pleural biopsy. Since the currently available tests for TP all have limitations in making a definitive diagnosis, clinicians urgently need new diagnostic tests. Objective: The study intended to compare the value in clinically diagnosing TP of the paraffin-embedded sample test (PEST), using pleural-effusion samples; an adenosine deaminase assay (ADA) using pleural fluid; and the T cell enzyme-linked immunospot test (T-SPOT), using peripheral-blood. Design: The research team performed a retrospective observational study. Setting: The study took place at the Sir Run Run Hospital, Nanjing Medical University in Nanjing, Jiangsu, China. Participants: Participants were 37 patients with suspected TP who had been admitted to the hospital between September 2018 and December 2022. Outcome Measures: The research team assessed the diagnostic performance of PEST, ADA, and T-SPOT in the TP group, calculating the positive rate, sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) of the tests. Results: Among the 37 participants, the testing confirmed that 24 had TP (64.86%), with 13 not having TP (35.14%). The PEST test produced a sensitivity of 83.3% for TP, with 20 out of 24 participants in the TP group testing positive (95% CI: 61.8 to 94.5), which was superior to the ADA, with only 9 out of the 24 participants (37.5%) in the TP group testing positive (95% CI: 19.6 to 59.2), with P < .001. Conclusions: The PEST test possesses a high diagnostic value, and clinicians can use it as a time-saving, noninvasive, and highly sensitive method for TP diagnosis. It can be adjunct method to the currently used tests for diagnosing TP. A combination of several detection methods could promote effective treatment.

Bloodstream infection and pneumonia caused by Chlamydia abortus infection in China: a case report.

BACKGROUND: Chlamydia abortus is generally considered to cause abortion, stillbirth, and gestational sepsis in pregnant women, but it's rare in bloodstream infection and pneumonia. CASE PRESENTATION: We present details of a patient with bloodstream infection and pneumonia caused by Chlamydia abortus. Both blood next-generation sequencing (NGS) and sputum NGS indicate Chlamydia abortus infection. The patient received intravenous infusion of piperacillin sodium and tazobactam sodium (4.5 g/8 h) and moxifloxacin (0.4 g/d) and oral oseltamivir (75 mg/day). Within one month of follow-up, the patient's clinical symptoms were significantly improved, and all laboratory parameters showed no marked abnormality. However, chest computer tomography (CT) showed the inflammation wasn't completely absorbed. And we are still following up. CONCLUSIONS: Chlamydia abortus can cause pneumonia in humans. NGS has the particular advantage of quickly and accurately identifying the infection of such rare pathogens. Pneumonia is generally not life-threatening, and has a good prognosis with appropriate treatment. However, Chlamydia infection can lead to serious visceral complications which clinicians should pay attention to.

Clinical characteristics of moderate COVID-19 patients aggravation in Wuhan Stadium Cabin Hospital: A 571 cases of retrospective cohort study.

To report the clinical characteristics and potential risk factors of patients with coronavirus disease 2019 (COVID-19) in Wuhan Stadium Cabin Hospital in Hubei Province. A total of 571 patients of COVID-19 treated in the Wuhan Stadium Cabin Hospital were selected for analysis, univariable and multivariable logistic regression methods were used to explore the risk factors associated with disease aggravation. The main clinical symptoms of moderate COVID-19 were fever, cough and dyspnea, hypertension, diabetes, and coronary heart diseases were the main comorbidities both in transferred and stable patients. Twenty-six patients (4.55%) of mild and moderate patients had disease aggravation, and most of which occurred between 36 and 48 hours after admission. Multiple regression analysis showed increasing odds of disease aggravation associated with former smoker history, diabetes, dyspnea, consolidation, and interstitial abnormalities of computed tomography scanning, lymphopenia and elevated of C-reactive protein, the time points of transferred patients mainly between 36 and 48 hours (65.38%), and the average hospital stay for stable patients was 15 days.It could help clinicians to identify patients with poor prognosis at an early stage, and provide early warning role for timely intervention.

The role of mitophagy in the mechanism of genioglossal dysfunction caused by chronic intermittent hypoxia and the protective effect of adiponectin.

PURPOSE: Dysfunction of the genioglossus muscle is important in the pathogenesis of obstructive sleep apnea due to chronic intermittent hypoxia (CIH). Mitochondrial impairment resulting from hypoxia is mitigated by mitophagy to avoid cell apoptosis in cardiomyocytes. This project was designed to explore the effects of CIH on mitophagy in the genioglossus muscle and the impact of adiponectin (Ad). METHODS: One hundred eighty male SD rats were randomly divided into 3 groups (normal control [NC], CIH, and CIH + Ad groups), with 60 rats in each group observed for 5 weeks. Comparisons of serum Ad levels, mitochondrial structure and function, mitophagy, and cell apoptosis in the genioglossus were made at different time points. RESULTS: (1) The CIH group was significantly different from the NC group as follows: During the first 3 weeks, serum Ad levels, the reactive oxygen species (ROS), relative proteins and mRNA of mitophagy, autophagy biomarker LC3-II, and autophagosomes increased, while during the last 2 weeks, most parameters decreased. (2) There was no difference among the 3 groups in mitochondrial structure and function-associated mRNA during the first 3 weeks, while damaged mitochondrial structures were growing during the last 2 weeks. Exacerbation of apoptosis was also detected in the last 2 weeks. (3) All of the damage was partially alleviated in the CIH + Ad group in contrast to CIH group at the end of this study. CONCLUSION: Disturbances of genioglossal mitophagy could be related to damaged mitochondrial structure and function induced by CIH, which could be alleviated by supplementation of exogenous Ad via increasing mitophagy.

First report of sparganosis manifested by pleuritis and decreased peripheral blood eosinophils in Jiangsu province, China.

Sparganosis is a parasitic infection caused by the metacestode stage of Spirometra mansoni and some other related diphyllobothriidean cestodes. Although various internal organs were involved in sparganum infection, pulmonary and pleural involvement is rarely reported. We herein report an uncommon form of sparganosis manifested by pleuritis and decreased peripheral blood eosinophils. Sparganum worms were found in the pleural effusion accidentally and confirmed by pathological diagnosis. After being treated with praziquantel for 10 days, the patient's symptoms, laboratory examinations, and imaging findings were improved gradually.

8-Hydroxy-2'-deoxyguanosine as a biomarker of oxidative stress in acute exacerbation of chronic obstructive pulmonary disease

Background/aim: 8-Hydroxy-2'-deoxyguanosine (8-OHdG) is a biomarker of oxidative stress and has been implicated in many diseases. The aim of this study was to investigate the clinical value of plasma 8-OHdG level in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Materials and methods: A total of 154 subjects were enrolled in this study, including 20 healthy volunteers, 24 COPD patients in the stable phase, and 110 AECOPD patients. Peripheral blood samples, demographic information, and clinical characteristics were collected from all subjects at the time of being recruited into the study. Plasma 8-OHdG level was detected by enzyme-linked immunosorbent a ss ay. Results: 8-OHdG was increased in patients with AECOPD compared to healthy subjects and patients with stable COPD, especially in smokers. It also increased with the GOLD stage, mMRC grade, CAT score, and group level of combined COPD assessment. Additionally, further analysis revealed that 8-OHdG was negatively correlated with FEV1, FEV1% predicted, and FEV1/FVC and positively correlated with C-reactive protein, procalcitonin, and neutrophil CD64. Conclusion: 8-OHdG is associated with spirometric severity, symptomatic severity, exacerbation risk, and inflammatory biomarkers in AECOPD patients, suggesting it as a promising biomarker for reflecting disease severity and guiding the choice of optimal therapeutic decision.

[Effects of chrysin on steroid-resistant asthma in a murine model].

OBJECTIVE: To explore the therapeutic effects of chrysin for steroid-resistant asthma in a murine model. METHODS: Lipopolysaccharide (LPS) was used to induce steroid-resistant asthma in a murine model sensitized and challenged with ovalbumin (OVA). Forty-eight female BALB/c mice were randomly divided into 6 groups of control (A), OVA (B), LPS + OVA (C), LPS + OVA + dexamethasone (D), LPS + OVA + chrysin (E) and LPS + OVA + dexamethasone + chrysin (F) (n = 8 each). At Day 1 and 14, group A received an intraperitoneal injection of phosphate buffered saline (PBS); groups B, C, D, E and F had an intraperitoneal injection of a mixture of OVA (20 µg) and aluminum hydroxide for sensitization. At Day 27, groups A and B were intranasally instilled with PBS while groups C, D, E and F had an intranasal instillation of LPS (10 µg). At Days 28, 29 and 30, groups B, C, D, E and F were challenged via airway with 1% OVA in PBS for 30 min and group A with PBS. Group D was intraperitoneally injected with dexamethasone (3 mg/kg) 30 min pre-challenge and PBS one day pre-challenge; group E received an intraperitoneal injection of chrysin (50 mg/kg) at one day and 1h pre-challenge; group F received dexamethasone (3 mg/kg) 30 min pre-challenge and chrysin (50 mg/kg) at one day and 1 h pre-challenge; groups A, B and C had PBS as above. Hematoxylin-eosin (HE) staining and periodic acid-Schiff (PAS) staining of lung tissues were performed to observe the pathologic changes. The total cells in bronchoalveolar lavage fluid (BALF) were counted under microscope. And enzyme-linked immunosorbent assay (ELISA) was applied for detecting interleukin-4 (IL-4) and interleukin-13 (IL-13) in BALF and IgE in sera. RESULTS: The inflammatory infiltration in lung tissue of group F was obviously suppressed compared with that of group C. The numbers of PAS-positive cells per bronchus divided by the total number of epithelial cells in group D, E, F were markedly lower than that in group C ((54.5 ± 6.9)%, (53.3 ± 8.2)%, (23.8 ± 7.0)% vs (71.3 ± 12.2)%, all P < 0.01). The total cells in BALF of group E and F significantly decreased versus that of group C ((1.22 ± 0.23) × 104/ml, (0.98 ± 0.25) × 104/ml vs (2.56 ± 0.18) × 104/ml, both P < 0.01). The levels of IL-4 in group D and F were significantly less than that of group C ((118 ± 7), (124 ± 5) vs (138 ± 6) pg/ml, both P < 0.01). The levels of IL-13 in BALF of group E and F significantly decreased compared with that of group C ((787 ± 57), (484 ± 32) vs (1 121 ± 132) pg/ml, both P < 0.01). The levels of IgE in sera of group D, E, F were significantly lower those of group C ((10 310 ± 494), (10 771 ± 650), (7 529 ± 485) vs (12 618 ± 595) ng/ml, all P < 0.01). CONCLUSION: Chrysin could improve the therapeutic efficacies of glucocorticoid for steroid-resistant asthma.

[Risk factors of bloodstream infections caused by Enterobacteriaceae and related prognostic factors in general intensive care unit].

OBJECTIVE: To explore the risk factors and its related prognostic factors of hospital-acquired bloodstream infections caused by enterobacteriaceae in general intensive care unit (GICU). METHODS: The clinical data of hospital-acquired bloodstream infections caused by enterobacteriaceae in general intensive care unit from January 2007 to December 2012 were retrospectively analyzed to determine the risk factors and explore the related prognostic factors of bloodstream infections by mono-factor and Logistic regression analysis. RESULTS: There were 35 cases BSI caused by enterobacteriaceae in all 96 patients with hospital-acquired bloodstream infections and the mortality was 42.9% (n = 15). The relevant risk factors included acute pancreatitis, abdominal surgery and use of antacids (P < 0.05 or 0.01) after a comparison of baseline conditions and clinical characteristics of patients between BSI caused by enterobacteriaceae and non-enterobacteriaceae. And the single factor and multi-factor Logistic regression analysis showed that their prognostic factors included patient age, acute physiology and chronic health evaluation (APACHE) II score, tracheal intubation or incision and extended-spectrum beta-lactamase (ESBL) positive (P < 0.05). CONCLUSION: The patients admitted into general intensive care unit with acute pancreatitis, abdominal surgery and use of antacids are more likely to suffer from EBSI. And patient age, APACHE II score, tracheal intubation or incision and ESBL are important prognostic factors.

The predictive value of delta-like3 and serum NSE in evaluating chemotherapy response and prognosis in patients with advanced small cell lung carcinoma: An observational study.

Lung cancer is one of the most malignant tumors with fastest morbidity and mortality. Small cell lung cancer (SCLC) is the most malignant pathological type of lung cancer with early metastasis and poor prognosis. At present, there is a lack of effective indicators to predict prognosis of SCLC patients. Delta-like 3 protein (DLL3) is selectively expressed on the surface of SCLC and is involved in proliferation and invasion. Neuron-specific enolase (NSE) is an enolase isoenzyme that is generally regarded as a biomarker for SCLC and may correlate with stage of SCLC, prognosis and chemotherapy response. NSE can be influenced by different types of factors. To explore the associations between expression levels of DLL3 in tumor tissues with platinum/etoposide chemotherapy response, and assess the prognostic values of DLL3, NSE and other potential prognostic factors in advanced SCLC patients were herein studied. Ninety-seven patients diagnosed with SCLC in Zhongda Hospital from 2014 to 2020 were enrolled in the study. Serum NSE levels were tested using ELISA methods before any treatment. The expression of DLL3 in tumor tissue was detected by Immunohistochemistry (IHC). We investigated the relationship of DLL3 expression with chemotherapy and survival. Progression free survival (PFS) and overall survival (OS) were estimated by the Kaplan-Meier method. Multivariate Cox-proportional hazard regression was used to identify predictors of PFS and OS. DLL3 was detected in 84.5% (82/97) of all patients' tumor samples by IHC, mainly located on the surface of SCLC cells. Lower DLL3 expression was associated with longer PFS and better chemotherapy response. OS had no significant differences. Multivariate analysis by Cox Hazard model showed that, high DLL3 expression and maximum tumor size >5 cm were independent risk factors for PFS, where NSE < 35 ng/mL and age < 70 were independent prognostic factors for OS. Early stage was independent prognostic factors for PFS and OS (P < .05 log-rank). DLL3 was expressed in the most of SCLCs. DLL3 expression level in the tumor and NSE level in the serum may be useful biomarkers to predict the prognosis of SCLC. DLL3 may be a potential therapeutic target for SCLC in the future.

Biomimetic Metal-Organic Framework Gated Nanoplatform for Sonodynamic Therapy against Extensively Drug Resistant Bacterial Lung Infection.

Novel antimicrobial strategies are urgently needed to treat extensively drug-resistant (XDR) bacterial infections due to the high mortality rate and lack of effective therapeutic agents. Herein, nanoengineered human umbilical cord mesenchymal stem cells (hUC-MSCs), named PMZMU, are designed as a sonosensitizer for synergistic sonodynamic-nano-antimicrobial therapy against gram-negative XDR bacteria. PMZMU is composed of a bacterial targeting peptide (UBI29-41) modified hUC-MSCs membrane (MSCm), a sonosensitizer meso-tetra(4-car-boxyphenyl) porphine doped mesoporous organo-silica nanoparticle and an acidity-responsive metal-organic framework ZIF-8. This innovative formulation enables efficient loading of polymyxin B, reduces off-target drug release, increases circulation and targeting efficacy, and generates reactive oxygen species upon ultrasound irradiation. PMZMU exhibits remarkable in vitro inhibitory activity against four XDR bacteria: Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa (PA), and Escherichia coli. Taking advantage of the bacterial targeting ability of UBI29-41 and the inflammatory chemotaxis of hUC-MSC, PMZMU can be precisely delivered to lung infection sites thereby augmenting polymyxin B concentration. PMZMU-mediated sonodynamic therapy significantly reduces bacterial burden, relieves inflammatory damage by promoting the polarization of macrophages toward M2 phenotype, and improves survival rates without introducing adverse events. Overall, this study offers promising strategies for treating deep-tissue XDR bacterial infections, and guides the design and optimization of biomimetic nanomedicine.

Mendelian randomization reveals no correlations between herpesvirus infection and idiopathic pulmonary fibrosis.

BACKGROUND: Previous studies have found that the persistence of herpesvirus significantly increases the risk of idiopathic pulmonary fibrosis (IPF), but it is unclear whether this effect is causal. We conducted a two-sample Mendelian randomization (MR) study to evaluate the causal relationship between three herpesvirus infections and IPF. METHODS: We used genome-wide association studies (GWAS) data from three independent datasets, including FinnGen cohort, Milieu Intérieur cohort, and 23andMe cohort, to screen for instrumental variables (IVs) of herpesvirus infection or herpesvirus-related immunoglobulin G (IgG) levels. Outcome dataset came from the largest meta-analysis of IPF susceptibility currently available. RESULTS: In the FinnGen cohort, genetically predicted Epstein-Barr virus (EBV) (OR = 1.105, 95%CI: 0.897-1.149, p = 0.815), cytomegalovirus (CMV) (OR = 1.073, 95%CI: 0.926-1.244, p = 0.302) and herpes simplex (HSV) infection (OR = 0.906, 95%CI: 0.753-1.097, p = 0.298) were not associated with the risk of IPF. In the Milieu Intérieur cohort, we found no correlations between herpesvirus-related IgG EBV nuclear antigen-1 (EBNA1) (OR = 0.968, 95%CI: 0.782-1.198, p = 0.764), EBV viral capsid antigen (VCA) (OR = 1.061, 95CI%: 0.811-1.387, p = 0.665), CMV (OR = 1.108, 95CI%: 0.944-1.314, p = 0.240), HSV-1 (OR = 1.154, 95%CI: 0.684-1.945, p = 0.592) and HSV-2 (OR = 0.915, 95%CI: 0.793-1.056, p = 0.225) and IPF risk. Moreover, in the 23andMe cohort, no evidence of associations between mononucleosis (OR = 1.042, 95%CI: 0.709-1.532, p = 0.832) and cold scores (OR = 0.906, 95%CI: 0.603-1.362, p = 0.635) and IPF were found. Sensitivity analysis confirmed the robustness of our results. CONCLUSIONS: This study provides preliminary evidence that EBV, CMV, and HSV herpesviruses, and herpesviruses-related IgG levels, are not causally linked to IPF. Further MR analysis will be necessary when stronger instrument variables and GWAS with larger sample sizes become available.

Hybrid stent in management of malignant airway obstruction with carina esophageal fistula: A case report.

RATIONALE: Airway stents have been developed rapidly to treat airway stenosis and fistula caused by various reasons. Malignant conditions that lead to central airway obstruction, especially the invasion of trachea carina and formation of esophageal fistula, are still a challenge for clinicians. PATIENT CONCERNS: A 61-year-old man presented with malignant airway obstruction and fistula between trachea carina and esophagus accompanied by severe respiratory failure. DIAGNOSIS: The patient was clinically diagnosed with esophageal squamous cell cancer of stage IV, carina esophageal fistula, severe pneumonia, hypoproteinemia. INTERVENTIONS: Y-shaped covered metallic stent and Y-type silicone stent (hybrid stent) were placed in the airway to increase tracheal patency, block the fistula and perform carinal plasty. OUTCOMES: The clinical symptoms of the patient improved rapidly and the lung infection was controlled effectively. This patient was followed up for more than 2 month, and the quality of life was better than before. LESSONS: Hybrid stent can be used as 1 of options for airway reconstruction and palliative treatment for patients with complex airway diseases caused by malignant tumors.

Plant-derived extracellular vesicles -a novel clinical anti-inflammatory drug carrier worthy of investigation.

Plant-derived extracellular vesicles (PDEVs) have shown remarkable potential as sustainable, green, and efficient drug delivery nanocarriers. As natural nanoparticles containing lipids, protein, nucleic acids and secondary metabolites, they have received widespread attention as a replacement for mammalian exosomes in recent years. In this review, the advances in isolation, identification, composition, therapeutic effect, and clinical application prospect were comprehensively reviewed, respectively. In addition, the specific modification strategies have been listed focusing on the inherent drawbacks of the raw PDEVs like low targeting efficiency and poor homogeneity. With emphasis on their biology mechanism in terms of immune regulation, regulating oxidative stress and promoting regeneration in the anti-inflammatory field and application value demonstrated by citing some typical examples, this review about PDEVs would provide a broad and fundamental vision for the in-depth exploration and development of plant-derived extracellular vesicles in the in-vivo anti-inflammation and even other biomedical applications.

Associations between diet and incidence risk of lung cancer: A Mendelian randomization study.

Background: Observational studies have revealed associations between diet and lung cancer. However, it is unclear whether the association is disturbed by confounding factors. We used a two-sample Mendelian randomization (MR) method to characterize the associations between diet and the lung cancer risk (including 3 subtypes: lung adenocarcinoma (LA), squamous cell lung carcinoma (SqCLC), and small cell lung cancer (SCLC)). Materials and methods: Data on 20 diets were screened from the UK Biobank. Lung cancer data came from a large meta-analysis of 85,716 individuals. The inverse-variance weighted method was used as the main analysis. Sensitivity analysis was also used to explain the different multiplicity patterns of the final model. Results: Our results showed significant evidence that 3 diets were associated with lung cancer [odds ratio (OR): 0.271, 95% confidence interval (CI): 0.150-0.488, p = 1.46 × 10-4, dried fruit; OR: 3.010, 95% CI: 1.608-5.632, p = 5.70 × 10-4, beer] and SqCLC (OR: 0.135, 95% CI: 0.062-0.293, p = 2.33 × 10-5, dried fruit; OR: 0.485, 95% CI: 0.328-0.717, p = 2.9 × 10-4, cheese). There were also suggestive correlations between 5 dietary intakes and lung cancer (OR: 0.441, 95% CI: 0.250-0.778, p = 0.008, cereal; OR: 2.267, 95% CI: 1.126-4.564, p = 0.022, beef), LA (OR: 0.494, 95% CI: 0.285-0.858, p = 0.012, dried fruit; OR: 3.536, 95% CI: 1.546-8.085, p = 0.003, beer) and SCLC (OR: 0.006, 95% CI: 0.000-0.222, p = 0.039, non-oily fish; OR: 0.239, 95% CI: 0.086-0.664, p = 0.006, dried fruit). No other association between diet and lung cancer was observed. Conclusion: Our study preliminary found that cheese, dried fruit, and beer intake were significantly associated with the risk of lung cancer or its subtypes, while cereal, beef, and non-oily fish intake were suggestively associated with the risk of lung cancer or its subtypes. Well-designed prospective studies are still needed to confirm our findings in the future.

Nucleus-Targeting Manganese Dioxide Nanoparticles Coated with the Human Umbilical Cord Mesenchymal Stem Cell Membrane for Cancer Cell Therapy.

Recently, development of drug delivery systems for accurate delivery of antitumor drugs to tumor sites to improve their antitumor efficacy has attracted great interest in the area of cancer immunotherapy. In this report, an intelligent biodegradable hollow manganese dioxide (HMnO2) nanoparticle (NP) with a human umbilical cord mesenchymal stem cell (hUC-MSC) membrane coating was designed to exert efficient chemo-immunotherapy for cancer treatment. A TAT peptide-modified membrane structure was constructed for nuclear targeting. Our findings showed that this new nanoreactor inherited the active targeting capability of MSCs and exhibited tumoritropic accumulation significantly at the cancerous parts. Compared with other formulations, intravenous injection of the NPs markedly inhibited tumor growth, relapse, and metastasis. Moreover, we found that the NPs effectively boosted dendritic cell maturation and recruited effector T cells into tumors. Overall, this work demonstrates the great potential of applying MSC membrane-coated manganese dioxide NPs as nucleus-targeting nanocarriers in cancer chemo-immunotherapy.

Clinical values of metagenomic next-generation sequencing in patients with severe pneumonia: a systematic review and meta-analysis.

Background: Clinical values of metagenomic next-generation sequencing (mNGS) in patients with severe pneumonia remain controversial. Therefore, we conduct this meta-analysis to evaluate the diagnostic performance of mNGS for pathogen detection and its role in the prognosis of severe pneumonia. Methods: We systematically searched the literature published in PubMed, Embase, Cochrane Library, Web of Science, Clinical Trials.gov, CNKI, Wanfang Data, and CBM from the inception to the 28th September 2022. Relevant trials comparing mNGS with conventional methods applied to patients with severe pneumonia were included. The primary outcomes of this study were the pathogen-positive rate, the 28-day mortality, and the 90-day mortality; secondary outcomes included the duration of mechanical ventilation, the length of hospital stay, and the length of stay in the ICU. Results: Totally, 24 publications with 3220 patients met the inclusion criteria and were enrolled in this study. Compared with conventional methods (45.78%, 705/1540), mNGS (80.48%, 1233/1532) significantly increased the positive rate of pathogen detection [OR = 6.81, 95% CI (4.59, 10.11, P < 0.001]. The pooled 28-day and 90-day mortality in mNGS group were 15.08% (38/252) and 22.36% (36/161), respectively, which were significantly lower than those in conventional methods group 33.05% (117/354) [OR = 0.35, 95% CI (0.23, 0.55), P < 0.001, I2 = 0%] and 43.43%(109/251) [OR = 0.34, 95% CI (0.21, 0.54), P < 0.001]. Meanwhile, adjusted treatment based on the results of mNGS shortened the length of hospital stay [MD = -2.76, 95% CI (- 3.56, - 1.96), P < 0.001] and the length of stay in ICU [MD = -4.11, 95% CI (- 5.35, - 2.87), P < 0.001]. Conclusion: The pathogen detection positive rate of mNGS was much higher than that of conventional methods. Adjusted treatment based on mNGS results can reduce the 28-day and 90-day mortality of patients with severe pneumonia, and shorten the length of hospital and ICU stay. Therefore, mNGS advised to be applied to severe pneumonia patients as early as possible in addition to conventional methods to improve the prognosis and reduce the length of hospital stay.

Analysis of the correlation between BMI and respiratory tract microbiota in acute exacerbation of COPD.

Objective: To investigate the distribution differences in the respiratory tract microbiota of AECOPD patients in different BMI groups and explore its guiding value for treatment. Methods: Sputum samples of thirty-eight AECOPD patients were collected. The patients were divided into low, normal and high BMI group. The sputum microbiota was sequenced by 16S rRNA detection technology, and the distribution of sputum microbiota was compared. Rarefaction curve, α-diversity, principal coordinate analysis (PCoA) and measurement of sputum microbiota abundance in each group were performed and analyzed by bioinformatics methods. Results: 1. The rarefaction curve in each BMI group reached a plateau. No significant differences were observed in the OTU total number or α-diversity index of microbiota in each group. PCoA showed significant differences in the distance matrix of sputum microbiota between the three groups, which was calculated by the Binary Jaccard and the Bray Curtis algorithm. 2. At the phylum level, most of the microbiota were Proteobacteria, Bacteroidetes Firmicutes, Actinobacteria, and Fusobacteria. At the genus level, most were Streptococcus, Prevotella, Haemophilus, Neisseria and Bacteroides. 3. At the phylum level, the abundance of Proteobacteria in the low group was significantly higher than that in normal and high BMI groups, the abundances of Firmicutes in the low and normal groups were significantly lower than that in high BMI groups. At the genus level, the abundance of Haemophilus in the low group was significantly higher than that in high BMI group, and the abundances of Streptococcus in the low and normal BMI groups were significantly lower than that in the high BMI group. Conclusions: 1. The sputum microbiota of AECOPD patients in different BMI groups covered almost all microbiota, and BMI had no significant association with total number of respiratory tract microbiota or α-diversity in AECOPD patients. However, there was a significant difference in the PCoA between different BMI groups. 2. The microbiota structure of AECOPD patients differed in different BMI groups. Gram-negative bacteria (G-) in the respiratory tract of patients predominated in the low BMI group, while gram-positive bacteria (G+) predominated in the high BMI group.