Aging is the predominant risk factor for several chronic disorders; therefore, elucidating the molecular and cellular mechanisms underlying age-related pathologies is essential for therapeutic advancement. Micheliolide (MCL), a naturally occurring guaianolide sesquiterpene lactone derived from Michelia champaca and Michelia compressa, has attracted increasing attention for its pharmacological potential. Its derivative, ACT001, enables the sustained release of MCL into the plasma in vivo, thereby enhancing oral bioavailability and improving therapeutic efficacy. ACT001 has recently received orphan drug designation for glioblastoma treatment, highlighting its clinical feasibility and safety profile. Increasing evidence indicates that MCL regulates age-related diseases by modulating inflammation, cell cycle, mitochondrial dysfunction, oxidative stress, and autophagy. By targeting key signaling pathways, including NF-κB, STAT3, NRF2, AMPK, and NLRP3, MCL/ACT001 demonstrated its protective effect against age-related diseases. This paper summarizes the current mechanistic insight and disease-specific evidence regarding MCL/ACT001 and further evaluates their therapeutic repositioning potential for age-related diseases, including cardiovascular and cerebrovascular diseases, fibrotic conditions, immune disorders, metabolic diseases, and tumors. Additionally, we discussed key translational challenges.

Background and Objective:Aspiration syndrome is a common respiratory disease in clinical practice. We hypothesized that bronchoalveolar lavage fluid (BALF) α-amylase might be a diagnostic biomarker for aspiration syndrome. Methods:This pilot, multicenter prospective study reviewed consenting adults who underwent clinically-indicated bronchoscopy at six hospitals. BALF samples were obtained using standardized methods. Amylase levels were measured in clinical biochemical laboratory. Aspiration syndrome was clinically diagnosed based on the Expert Task Force on Diagnosis And Treatment of Aspiration Pneumonia in Adults in China (2022) and the guidelines of the Japanese Respiratory Society. Results:Among 248 participants, 159 met clinical criteria for aspiration. The median level of BALF α-amylase in cases was significantly higher than that in controls (2884.2 IU/L vs 30.0 IU/L, P < 0.001). The optimal cut-off was 179.1 IU/L (sensitivity 87.4%, specificity 93.3%, AUC 0.937, 95% CI 0.905-0.970). Subgroup analysis stratified by sex (male or female) and age (< 60 or ≥ 60 years) showed that the specificity and sensitivity remained above 0.80. Conclusion:BALF α-amylase might be a promising biomarker for distinguishing aspiration syndrome.

Purpose:Burkholderia multivorans, a Gram-negative bacterium, often infect patients with severe immunocompromised and cystic fibrosis. B. multivorans infection is challenging to treat due to its ability to disrupt the action of multiple antimicrobial agents through intrinsic and acquired resistance mechanisms. A better understanding of the pulmonary microbial spectrum of B. multivorans infection is crucial for the prevention and treatment of B. multivorans. Case presentation:This case series reviewed the respiratory microbiome structure and alternations during the treatment of B. multivorans infection through metagenomic next-generation sequencing (mNGS). Analysis of mNGS data of 19 pharyngeal secretion samples collected from the 3 COVID-19 patients at different time points showed that the relative abundance of B. multivorans was fluctuated and eventually increased, indicating the possible development of drug resistance. A total of 40 antibiotic-resistant genes (ARGs) were detected. Significantly, the levels of CEOA, CEOB, and OPCM were consistent with the trends in the relative abundance of B. multivorans. Besides, we described nine previously uncharacterized non-synonymous mutations in PenA of B. multivorans. These mutations lead to amino acid changes Thr32Ala, Ala43Ser, Gln105Arg, Asn202Ser, Gln219Arg, Gly241Ala, Val259Ala, Thr279Ala, and Ser298Ile that may associate with resistance to β-lactam antibiotics. Conclusion:This report shed light on the importance of rapidly diagnosis and treatment of B. multivorans infection. mNGS serve as a powerful microbial detection tool that provides a comprehensive, sensitive, and rapid method for pathogen detection and drug resistance analysis.

Metagenomic next-generation sequencing (mNGS) has become an available method for pathogen detection. The clinical application of mNGS requires further evaluation. We conducted a cross-sectional study of 104 patients with suspected infection between May 2019 and May 2021. The risk factors associated with infection were analyzed using univariate logistic analysis. The diagnostic performance of pathogens was compared between mNGS and conventional microbiological tests. About 104 patients were assigned into 3 groups: infected group (n = 69), noninfected group (n = 20), and unknown group (n = 15). With the composite reference standard (combined results of all microbiological tests, radiological testing results, and a summary of the hospital stay of the patient) as the gold standard, the sensitivity, specificity, positive predictive value, negative predictive value of mNGS was 84.9%, 50.0%, 88.6%, and 42.1%, respectively. Compared with conventional microbiological tests, mNGS could detect more pathogens and had obvious advantages in Mycobacterium tuberculosis, Aspergillus, and virus detection. Moreover, mNGS had distinct benefits in detecting mixed infections. Bacteria-fungi-virus mixed infections were the most common in patients with severe pneumonia. mNGS had a higher sensitivity than conventional microbiological tests, especially for M. tuberculosis, Aspergillus, viruses, and mixed infections. We suggest that mNGS should be used more frequently in the early diagnosis of pathogens in critically ill patients in the future.

Urinary Catheter-Related Vesicoileal Fistula A man with a 5-month history of urethral catheter use had sudden onset of turbid, greenish-yellow urine. CT showed protrusion of the catheter through the bladder wall, and a vesicoileal fistula was seen on laparoscopy (shown in a video).

Granuloma formation is generally correlated with infection. Pulmonary granulomas caused by foreign bodies aspiration are uncommon. The clinical and radiologic features of such cases often lack specificity, which makes it difficult to distinguish from malignancy. Aspiration is usually not considered in the differential diagnosis of patients presenting with mass-like abnormalities on chest imaging. Occult aspiration history, diverse clinical manifestations, atypical imaging findings, and limited availability of pathogen detection techniques make the precise diagnosis a substantial challenge. Herein, we describe an older patient presenting with chest pain and worrisome lung masses/nodules that proved to be pulmonary granulomas caused by foreign matters aspiration. In addition, the patient developed Mendelson syndrome due to acute macroaspiration. Lung tissue metagenomics next-generation sequencing (mNGS) revealed Streptococcus intermedius, a normal flora of the oropharynx. The aim of this case was to underscore the importance of considering aspiration as a potential differential diagnosis of patients presenting with pulmonary granulomas, especially in patients with recurrent pneumonia or predisposing factors. In addition, mNGS act as a potential, rapid, and effective technique for diagnosing aspiration-related syndrome, showing satisfactory performance in identifying pathogens.

Purpose:The detection of pathogenic microorganisms plays a significant role in the diagnosis and management of pneumonia that are responsible for a substantial number of deaths worldwide. However, conventional microbiological tests (CMT) have low accuracy and are time-consuming. In this study, we aim to evaluate the clinical value of Chips for Complicated Infection Detection (CCID) in detecting pneumonia pathogens. Patients and Methods:This study was conducted at nine hospitals in China from January 2021 to September 2022. Respiratory samples from adult pneumonia patients were collected from each patient. CMT and CCID were performed in parallel to identify the pathogens. Results:A total of 245 patients were included, with 73% being elderly. CCID identified pathogenic microbes in 78.0% of patients and conventional microbiological tests (CMT) in 57.1% of the patients (p<0.001). The overall positive and negative percent agreements between CCID and CMT for pathogen detection were 90.07% and 38.46%, respectively. 38.8% of patients were diagnosed with mixed infections with at least two pathogens by CCID. Bacterial infections identified by CCID accounted for 60.0% of 245 patients, with the top 3 being Pseudomonas aeruginosa, Klebsiella pneumoniae, and Enterococcus faecium, respectively. K. pneumoniae was the most common pathogen in elderly patients, with a significantly higher prevalence compared to non-elderly patients (p = 0.0011). Among the 197 patients who had used antibiotics before sample collection, the positive rate of CCID was significantly higher than that of CMT (p < 0.001). Conclusion:This study indicates that compared to CMT, this novel chip has significant advantages in detecting pathogens in pneumonia patients, especially in the elderly.

Purpose:Aspiration pneumonia (AP) challenges public health globally. The primary aim of this study was to ascertain the microbiological profile characteristics of patients with AP evaluated by combined detection methods, including conventional microbiological tests (CMTs), chips for complicated infection detection (CCID), and metagenomic next-generation sequencing (mNGS).Patients and Methods:From June 2021 to March 2022, a total of thirty-nine patients with AP or community-acquired pneumonia with aspiration risk factors (AspRF-CAP) from 3 hospitals were included. Respiratory specimens, including bronchoalveolar lavage fluid (BALF), sputum, and tracheal aspirate, were collected for microorganism detection.Results:Patients with AP were more inclined to be older, to have a shorter duration from illness onset to admission, to have a higher prevalence of different underlying diseases, particularly diabetes mellitus, chronic heart disease, and cerebrovascular disease, and to have a higher CURB-65 score (all P < 0.05). A total of 213 and 31 strains of microorganisms were detected in patients with AP and AspRF-CAP, respectively. The most common pathogens in AP were Corynebacterium striatum (17/213, 7.98%), Pseudomonas aeruginosa (15/213, 7.04%), Klebsiella pneumoniae (15/213, 7.04%), and Candida albicans (14/213, 6.57%). Besides, the most common pathogens in AspRF-CAP were Candida albicans (5/31, 16.13%), Pseudomonas aeruginosa (3/31, 9.68%) and Klebsiella pneumoniae (3/31, 9.68%). Moreover, Klebsiella pneumoniae (7/67, 10.45%) and Candida glabrata (5/67, 7.46%) were the most common pathogens among the 9 non-survived patients with AP.Conclusion:The prevalent pathogens detected in cases of AP were Corynebacterium striatum, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Candida albicans. Early combined detection methods for patients with AP enhance the positive detection rate of pathogens and potentially expedites the initiation of appropriate antibiotic therapeutic strategies.

Background Aspiration pneumonia (AP) is difficult to diagnose and has poor outcomes. This case-control study aimed to explore the risk factors and delineate the antibiotic usage for AP. Methods Inpatients diagnosed with community-acquired pneumonia (CAP) from 2013 to 2017, enrolled in the urban employee basic medical insurance program in Beijing, were included and classified into the AP (N = 2,885) and non-AP (N = 53,825) groups. Risk factors were identified by logistic regression. Results Older age (compared to 18–64 years, OR for 65–79 years: 4.3, 95% CI: 3.8–4.9; OR for >80 years: 6.3, 95% CI: 5.6–7.2), male (OR: 1.4, 95% CI: 1.3–1.5), cerebrovascular disease (OR: 3.1, 95% CI: 2.8–3.5), dementia (OR: 2.0, 95% CI: 1.8–2.1), vomiting (OR: 1.4, 95% CI: 1.2–1.7), Parkinson's disease (OR: 2.1, 95% CI: 1.8–2.4), and epilepsy (OR: 3.2, 95% CI: 2.8–3.7) were associated with an increased risk of AP. 92.8% of the AP patients received antibiotic therapy. Among them, patients treated with broad-spectrum antibiotics, antibiotics for injection, and combined antibiotics accounted for 93.3%, 97.9%, and 81.7%, respectively. Conclusions Older age, male, and several comorbidities were independent risk factors for AP, and combined antibiotics treatments are common, which merits attention in accurate detection of AP in a high-risk population.

Background Mycoplasma pneumoniae is an important infectious pathogen of lower respiratory tract infection in children and adolescents. Macrolide resistant M. pneumoniae (MRMP) has become increasingly prevalent, and identifying pathogen resistance genes is crucial for treatment. Case Presentation We report a patient with severe refractory M. pneumoniae pneumonia (MPP). The failure of initial clinical treatment prompted the re-analysis of metagenomic next-generation sequencing (mNGS) data for macrolide-resistant gene. Macrolide-resistance 23S ribosomal RNA gene was confirmed with read depth of 64 X for the A2063G mutation, which can decrease the affinity of macrolide with M. pneumoniae ribosome resulting in macrolide resistance. Furthermore, antimicrobial susceptibility testing demonstrated that M. pneumoniae was resistant to macrolide. PCR confirmatory test about M. pneumoniae resistance A2063G mutation, clinical treatment course and prognosis with altered treatment strategy, and M. pneumoniae antimicrobial susceptibility confirmed that the severe refractory MPP was due to macrolide resistant M. pneumoniae. Conclusion As a new molecular level detection, mNGS is an effective method for detecting M. pneumoniae resistance genes. Early recognition of macrolide resistance and suitable antibiotics strategy is of vital importance for the prognosis of severe refractory MPP.

起搏器囊袋感染是心脏植入装置术后感染类型之一,若不及时处理,会造成血行感染及感染性心内膜炎. 尤其对于高龄患者,一旦怀疑起搏器植入感染,亟需引起重视. 精准快速的病原学结果对于辅助诊断及调整抗感染方案具有重要意义. 本文对1例应用宏基因组二代测序技术及病原微生物芯片辅助病原学诊断起搏器导丝处皮肤破溃感染病例进行报道,为临床特殊病原体感染的诊疗提供参考.

Background: Detecting pathogens is crucial for management of pneumonia. Chips for Complicated Infection Detection (CCID), based on isothermal amplification technology and microfluidic technology, can simultaneously detect multi-target nucleic acid of 174 pathogens within 50 minutes. Aims: To evaluate the diagnostic value of CCID in detecting pneumonia pathogens. Methods: This study was conducted at nine hospitals in China from January 2021 to September 2022. Respiratory samples from adult pneumonia patients were collected to evaluate the diagnostic value of CCID. Results: A total of 245 patients were included, with 73.1% being elderly. The overall positive and negative percent agreements between CCID and conventional microbiological tests (CMT) for pathogen detection were 90.0% and 38.1%, respectively. CCID identified pathogenic microbes in 78.0% patients and CMT in 57.1% patients (p<0.001). 38.8% patients were diagnosed as mixed infections with at least two pathogens by CCID. Bacterial infections identified by CCID accounted for 44.1% of 245 patients, with top 3 being Pseudomonas aeruginosa, Klebsiella pneumoniae, and Enterococcus faecium, respectively. K. pneumoniae was the most common pathogen in elderly patients, with a significantly higher prevalence compared to non-elderly patients (p=0.0011). Among 197 patients who had used antibiotics before sample collection, the positive rate of CCID was significantly higher than that of CMT (p<0.001). Conclusion: CCID is effective in detecting pathogen of pneumonia and has promising clinical application prospect. This work was supported by National Key R&D Program of China (2020YFC2005401).

Community acquired pneumonia(CAP)is characterized by high morbidity and mortality in immunocompromised patients, with the elderly as the main vulnerable population.However, current guidelines in China and elsewhere do not offer specific recommendations on the diagnosis and treatment of such patients.This paper reviews the definition, classification, epidemiology, etiological characteristics, clinical manifestations, diagnosis, treatment and prognosis of CAP in immunocompromised elderly patients, to provide a theoretical framework for its diagnosis and treatment and for the formulation of guidelines.

Background: Aspiration has become an increasingly significant health issue worldwide due to high mortality and morbidity of aspiration-related lung diseases. Aspiration, however, is difficult to diagnose accurately due to lack of effective diagnostic biomarkers. Aims: To explore the diagnostic value of bronchoalveolar lavage fluid (BALF) amylase levels for aspiration. Methods: We conducted a multi-center cross-section study in 6 hospitals from January 2018 to December 2022. Participants were classified into two groups: aspiration group and control group. BALF amylase levels were measured by biochemical analyzer in clinical laboratory. The levels of amylase in BALF were compared by the Wilcoxon test. Results: Of 222 enrolled participants (151 cases and 71 controls) , the mean age was (68.7±13.7) years and (50.8±16.9) years, and there were 109 (72.7%) and 33 (46.5%) males for cases and controls, respectively. The median level of amylase in cases was significantly higher than those without aspiration [6795.6 (IQR, 537.0-8645.3) vs 53.7 (IQR,30.0-55.6) IU/L, P<0.001]. BALF amylase is predictive for diagnosing the patients with aspiration (AUC:0.956) with a high sensitivity (98.6%) and specificity (87.4%). BALF amylase specified at 179.1 IU/L was determined as the optimal threshold for distinguishing aspiration. Subgroup analysis stratified by age and sex showed that the specificity and sensitivity remained above 85.0%. Conclusions: BALF amylase level shows remarkable diagnostic value (cut-off value: 179.1IU/L) and might be a promising biomarker for distinguishing aspiration. This work was supported by National Key R&B Program of China (2020YFC2005401).

Objectives To assess the ability of procalcitonin (PCT)—a promising marker for coinfections—to predict coinfections in patients with COVID-19. Methods In this systematic review and meta-analysis, PubMed, Embase, Web of Science, Cochrane, the China National Knowledge Infrastructure (CNKI), and Wanfang were searched to identify eligible studies (up to August 30, 2021). Articles that reported the predictive value of PCT for coinfections in patients with COVID-19 were included. Individual and pooled sensitivities and specificities were reported, and I 2 was used to test heterogeneity. This study was prospectively registered on the International Prospective Register of Systematic Reviews (PROSPERO) database (registration number: CRD42021283344). Results Five studies involving a total of 2775 patients reported the predictive value of PCT for coinfections in patients with COVID-19. The sensitivity, specificity, and area under the curve of PCT in predicting coinfections in the pooled studies were 0.60 (95% CI 0.35–0.81, I 2 = 88.85), 0.71 (95% CI 0.58–0.81, I 2 = 87.82), and 0.72(95% CI 0.68–0.76) respectively. Conclusions Although PCT has limited predictive value for coinfections in patients with COVID-19, lower PCT levels seem to indicate a decreased probability of having a coinfection.

With the rising aging population, the number of people with stroke, dementia and Parkinson's disease is huge.These patients often have swallowing dysfunction, cognitive decline, decreased immune function, long-term bed rest, malnutrition, and sarcopenia, and are prone to pneumonia.However, the clinical manifestations of these patients with pneumonia are non-specific.The patients often cannot accurately express their complaints, resulting in symptoms being ignored.The underlying diseases of the nervous system increase the risk of pneumonia-related death, and is associated with poor prognosis.This article aimed to review the risk factors, prevention and treatment of these three neurological disorders complicated with pneumonia.

特发性肺纤维化(IPF)是一种原因不明的进行性和致命性间质性肺疾病.随着分子生物测序技术的发展和肺部微生态的研究,文献发现在IPF患者的肺泡灌洗样品中细菌负荷增加,与健康受试者相比,嗜血杆菌属、奈瑟菌属、链球菌属和韦荣球菌属丰度更高.研究表明肺部微生态失调可通过释放外膜囊泡,将抗原呈递给巨噬细胞,激活Toll样受体-Myd88-白细胞介素17B固有免疫通路来促进肺纤维化.本文总结肺部微生态在IPF中的作用,旨在为IPF靶向抗菌治疗和寻找免疫治疗靶点提供思路.

Abstract Background Aspiration-related lung disease may mimick a variety of pulmonary disorders. Complex clinical presentations, non-specific radiologic characteristics, lack of aspiration history and difficulties in obtaining lung biopsy make diagnosis challenging. Methods This retrospective observational study reviewed all patients of aspiration pneumonia identified on lung pathology in Peking university first hospital from January 1, 2010 to December 31, 2021.Clinical information including risk factors, symptoms, bronchoscopic examinations, chest imaging findings and outcomes on discharge were analyzed. Results A total of 20 inpatients with aspiration-related lung disease were included. Median age was 64 years (interquartile range: 55 to 67.75) and 14 (70%) were male patients. Aspiration-related lung disease was confirmed by lung biopsy (histologic presence of foreign body or other particulate matter) or cytologic pathology in BALF. Of these,19(95%) lung specimens included 6 (30%) surgical biopsy, 12 (60%) bronchoscopic biopsy and 1 CT-guided lung aspiration biopsy. One patient was identified by cytologic examination of BAL fluid. Recurrent cough was the most common symptom (70%). Four patients (20%) were asymptomatic and were discovered pulmonary nodules incidentally. Fourteen patients (70%) had one or more risk factors for aspiration, with dysphagia or choking the most common one (10 cases, 50%). Only 7 patients (35%) were clinically suspected of aspiration prior to biopsy. Twelve patients (66.7%) showed at least 2 lung lobes involved. Chest CT imaging revealed a variety of abnormalities, including mass in 9 patients (50%), ground glass opacity in 8 patients (44.4%), consolidation in 7 patients (38.9%), bronchiolitis in 5 patients (27.8%). The proportion of neutrophils in BALF cytological classification increased significantly during all 7 patients who underwent bronchoalveolar lavage. Five patients occurred respiratory failure and one patient needed endotracheal intubation for auxiliary ventilation. Conclusions Our study confirmed the atypical clinical manifestations of aspiration-related disease, which should be considered in the differentiation of pulmonary lesions even without risk factors or respiratory symptoms.