Single-cell profiling identifies T cell subsets associated with control of tuberculosis dissemination.

To identify T cell subsets associated with control of tuberculosis, single-cell transcriptome and T cell receptor sequencing were performed on total T cells from patients with tuberculosis and healthy controls. Fourteen distinct subsets of T cells were identified by unbiased UMAP clustering. A GZMK-expressing CD8+ cytotoxic T cell cluster and a SOX4-expressing CD4+ central memory T cell cluster were depleted, while a MKI67-expressing proliferating CD3+ T cell cluster was expanded in patients with tuberculosis compared with healthy controls. The ratio of Granzyme K-expressing CD8+CD161-Ki-67- and CD8+Ki-67+ T cell subsets was significantly reduced and inversely correlated with the extent of TB lesions in patients with TB. In contrast, ratio of Granzyme B-expressing CD8+Ki-67+ and CD4+CD161+Ki-67- T cells and Granzyme A-expressing CD4+CD161+Ki-67- T cells were correlated with the extent of TB lesions. It is concluded that granzyme K-expressing CD8+ T cell subsets might contribute to protection against tuberculosis dissemination.

Comparison of clinical and imaging features between pulmonary tuberculosis complicated with lung cancer and simple pulmonary tuberculosis: a systematic review and meta-analysis.

This review aimed to compare the clinical features and CT imaging features between patients with pulmonary tuberculosis (PTB) and lung cancer and patients with PTB alone. That would help to analyse the differences between the two and consequently providing a theoretical basis for the clinical diagnosis and treatment for the patients. Relevant case-control studies focusing on the clinical and CT imaging characteristics between PTB with lung cancer and PTB alone were systematically searched from five electronic databases. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for comparison. As of 2021-07-06, a total of 1735 articles were retrieved. But only 15 articles were finally included for meta-analysis. The results showed a higher proportion of irritable cough, haemorrhagic pleural effusion and lower proportion of night sweating in PTB patients with lung cancer than in PTB patients, and the differences were statistically significant (irritable cough: OR 2.43, 95% CI 1.43-4.11; haemorrhagic pleural effusion: OR 5.73, 95% CI 1.63-20.12; night sweating: OR 0.56, 95% CI 0.36-0.87). In addition, there are many differences in the imaging characteristics of the two types of patients. In conclusion, this review summarises the similarities and differences in clinical symptoms and imaging features between patients with PTB and lung cancer and patients with PTB alone, suggesting that we should be alert to the occurrence of lung cancer in patients with obsolete PTB relapse.

Identification of key genes associated with the progression of liver fibrosis to hepatocellular carcinoma based on iTRAQ proteomics and GEO database.

INTRODUCTION AND OBJECTIVE: Liver fibrosis (LF) often leads to cirrhosis and even hepatocellular carcinoma (HCC), but the molecular mechanism remains unclear. The aims of the present study were to identify potential biomarkers for the progression of LF to HCC and explore the associated molecular mechanisms. MATERIALS AND METHODS: The isobaric tags for relative and absolute quantitation (iTRAQ) was used to detect changes in the protein expression profiles of liver tissues and to screen the differentially expressed proteins (DEPs). The differentially expressed genes (DEGs) of LF rats and patients were screened by Gene Expression Database (GEO). Subsequently, the clinicopathological analysis of the overlapping genes in different pathological stages in HCC patients based on GEPIA database was conducted. RESULTS: iTRAQ proteomic analysis revealed 689, 749 and 585 DEPs in the 6W, 8W and 12W groups, respectively. ALDH2, SLC27A5 and ASNS were not only the DEPs found in rats with LF with different stages but were also the DEGs related to the pathological stages and survival in patients with HCC. CONCLUSIONS: ALDH2, SLC27A5 and ASNS were the potential biomarkers associated with the progression of LF to HCC.

High-dose rifampicin for the treatment of tuberculous meningitis: a meta-analysis of randomized controlled trials.

WHAT IS KNOWN AND OBJECTIVE: Tuberculous meningitis (TBM) is one of the most serious types of extrapulmonary tuberculosis and has caused distress to human. Effective treatment is particularly important. The aim of this meta-analysis is to compare the efficacy of high-dose and standard-dose rifampicin. METHODS: Databases including PubMed, Web of Science, Embase, Scopus and the Cochrane Library databases were electronically searched to identify randomized controlled trials that reported high-dose rifampicin in treatment of patients with TBM. The retrieval time is limited from inception to June 2021. Two reviewers independently screened literature, extracted data and assessed risk bias of included studies. Meta-analysis was performed by using STATA 12.0 software. RESULTS AND DISCUSSION: A total of 12 studies involving 1596 patients were included. The meta-analysis results showed no significant differences in 6-month mortality, 9-month mortality, Grade I-II AE, Grade III-V AE, hepatotoxicity, hepatotoxicity Grade I-II and cardiologic events between high-dose rifampicin (or high-dose rifampicin plus moxifloxacin or levofloxacin) and standard-dose groups. The log(Cmax ) (WMD 0.69, 95%CI 0.59-0.79, p 0.001) and log(AUC0-24h ) (WMD 0.79, 95%CI 0.71-0.88, p 0.001) were higher with high-dose rifampicin. Subgroup analysis revealed the rise of log(Cmax ) in high-dose rifampicin orally was consistent with intravenous administration compared with the control (WMD 0.69, 95%CI 0.66-0.73, p 0.001). WHAT IS NEW AND CONCLUSION: High-dose rifampicin was not a protective factor for 6-month mortality, despite increased plasma Cmax and AUC0-24h . However, the above conclusions are still required to be verified through more RCTs due to the limited quantity of included studies.

Anti-liver fibrosis effects of the total flavonoids of litchi semen on CCl4-induced liver fibrosis in rats associated with the upregulation of retinol metabolism.

CONTEXT: The litchi semen are traditional medications for treating liver fibrosis (LF) in China. The mechanism remains unclear. OBJECTIVE: This study investigates the anti-liver fibrotic mechanism of the total flavonoids of litchi semen (TFL). MATERIALS AND METHODS: Sprague-Dawley rats with carbon tetrachloride-induced LF were treated with TFL (50 and 100 mg/kg) for 4 weeks. The anti-liver fibrotic effects of TFL were evaluated and the underlying mechanisms were investigated via histopathological analysis, proteomic analysis and molecular biology technology. RESULTS: Significant anti-LF effects were observed in the high-TFL-dose group (TFL-H, p < 0.05). Five hundred and eighty-five and 95 differentially expressed proteins (DEPs) were identified in the LF rat model (M group) and TFL-H group, respectively. The DEPs were significantly enriched in the retinol metabolism pathway (p < 0.0001). The content of 9-cis-retinoic acid (0.93 ± 0.13 vs. 0.66 ± 0.10, p < 0.05, vs. the M group) increased significantly in the TFL-H group. The upregulation of RXRα (0.50 ± 0.05 vs. 0.27 ± 0.13 protein, p < 0.05), ALDH2 (1.24 ± 0.09 vs. 1.04 ± 0.08 protein, p < 0.05), MMP3 (0.89 ± 0.02 vs. 0.61 ± 0.12 protein, p < 0.05), Aldh1a7 (0.20 ± 0.03 vs. 0.03 ± 0.00 mRNA, p < 0.05) and Aox3 (0.72 ± 0.14 vs. 0.05 ± 0.01 mRNA, p < 0.05) after TFL treatment was verified. CONCLUSIONS: TFL exhibited good anti-liver fibrotic effects, which may be related to the upregulation of the retinol metabolism pathway. TFL may be promising anti-LF agents with potential clinical application prospects.

Exploratory development of PCR-fluorescent probes in rapid detection of mutations associated with extensively drug-resistant tuberculosis.

This study aims to evaluate the clinical value of PCR-fluorescent probes for detecting the mutation gene associated with extensively drug-resistant tuberculosis (XDR-TB). The molecular species identification of 900 sputum specimens was performed using polymerase chain reaction (PCR)-fluorescent probe. The mutations of the drug resistance genes rpoB, katG, inhA, embB, rpsL, rrs, and gyrA were detected. The conventional drug susceptibility testing (DST) and PCR-directed sequencing (PCR-DS) were carried out as control. DST demonstrated that there were 501 strains of rifampicin resistance, 451 strains of isoniazid resistance, 293 strains of quinolone resistance, 425 strains of streptomycin resistance, 235 strains of ethambutol resistance, and 204 strains of amikacin resistance. Furthermore, 427 (47.44%) or 146 (16.22%) strains were MDR-TB or XDR-TB, respectively. The mutations of the rpoB, katG, inhA, embB, rpsL, rrs, and gyrA genes were detected in 751 of 900 TB patients by PCR-fluorescent probe method, and the rate of drug resistance was 751/900 (83.44%). No mutant genes were detected in the other 149 patients. Compared with DST, the mutant rates of rpoB, katG/inhA, rpsL, rrs, embB, and gyrA of six drugs were higher than 88%; five of six drugs were higher than 90% except for SM (88.11%). The MDR and XDR mutant gene types were found in 398 (42.22%) and 137 (15.22%) samples. PCR-DS was also employed and confirmed the PCR-fluorescent probe method with the accordance rate of 100%. The PCR-fluorescent probe method is rapid and straightforward in detecting XDR-TB genotypes and is worthy of being applied in hospitals.

[Anti-inflammatory effect, plasma effective components and therapeutic targets of Huanglian Jiedu Decoction on ulcerative colitis mice].

This paper was to investigate the effect of Huanglian Jiedu Decoction(HLJD) on ulcerative colitis(UC) in mice, and determine the effective components in plasma, and virtually screen its therapeutic target, and predict its mechanism. Sixty Balb/c mice were randomly divided into blank group, model group, mesalazine treatment group(0.3 g·kg~(-1)), and HLJD treatment groups(24.66, 12.33, 6.17 g·kg~(-1)). Excepted for the blank group, all the mice in HLJD and mesalazine treatment groups were gavage administration. All mice freely drank 2.5% DSS solution for seven days to induce UC. The disease activity index(DAI) was detected each day. At the end of the experiment, HE staining was used to observe the pathological changes in colon. The content of IL-1ß, IL-6 and TNF-α in colon were determined by ELISA. The effective components in plasma were determined by UPLC-Q-TOF-MS. The reverse docking in PharmMapper was used to screen the component targets. The disease targets of UC were collected by searching TTD, OMIM and GeneCards databases. The intersection of the component targets and disease targets was selected as the therapeutic targets. Then the therapeutic targets were imported into the STRING for GO and KEGG enrichment analysis. Discovery Studio was used to simulate the docking between the components and the targets. RESULTS:: showed that the DAI in the model group increased significantly(P<0.05), and the number of inflammatory cells and infiltration degree increased significantly compared with the blank group. The DAI in HLJD treatment group was significantly reduced(P<0.05), and the number and infiltration degree of inflammatory cells were reduced compared with the model group. The ELISA results showed that the levels of IL-1ß, IL-6 and TNF-α were increased significantly in the model group(P<0.01) compared with the blank group, and significantly down regulated in the HLJD treatment group(P<0.05) compared with the model group. After UPLC-Q-TOF-MS analyse, ten components were identified. The network pharmacology analysis showed that the action targets were significantly enriched in 129 of biological processes, such as response to organic substance, chemical and oxygen-containing compound, etc., as well as 16 of signal pathways, such as IL-17, TNF and hepatitis B signal pathways, were enriched too. The results of molecular docking showed that limonin, palmatine and berberine could bind to CASP3 and MMP9 by hydrogen bond. In conclusion, HLJD could alleviate the colonic mucosal inflammatory infiltration and mucosal damage in UC mice. The mechanism may be related to the anti-inflammatory effect on UC mice by reducing the levels of IL-1ß, IL-6 and TNF-α in colon through limonin, palmatine and berberine regulating IL-17 signal pathway and TNF signal pathway via CASP3 and MMP9 meditated.

[Effect and mechanism of total flavonoids of Lichi Semen on CCl_4-induced liver fibrosis in rats, and prediction of Q-marker].

This paper was to investigate the effect of total flavonoids of Lichi Semen(TFL) on carbon tetrachloride(CCl_4)-induced liver fibrosis in rats, analyze and predict its mechanism of action and potential quality markers(Q-marker). Firstly, male SD rats were taken and injected subcutaneously with a 40% CCl_4-vegetable oil solution twice a week for 8 consecutive weeks to establish a rat model of liver fibrosis. The rats with liver fibrosis were randomly divided into model group, silybin group(43.19 mg·kg~(-1)), Fuzheng Huayu Capsules group(462.75 mg·kg~(-1)), and TFL groups(100 mg·kg~(-1) and 25 mg·kg~(-1)), with normal rats as a blank group, 10 rats in each group. Except for the blank group, the rats in the other groups were subcutaneously injected with 40% CCl_4-vegetable oil solution of a maintenance dose, once a week. The rats in various treatment groups received corresponding doses of drugs, while the rats in the blank group and model group received the same volume of normal saline once a day for 4 weeks. At the end of the experiment, blood was collected from the abdominal aorta and the liver tissues were collected. The levels of total bilirubin(TBiL), direct bilirubin(DBiL), indirect bilirubin(IBiL), alanine aminotransferase(ALT), and aspartate aminotransferase(AST) in serum were detected by using an automatic biochemical detector. Masson staining was used to observe the histopathological changes of rat liver. Then, the chemical compositions of TFL were collected, and the action targets of these chemical compositions were predicted through SWISS database and reverse molecular docking server(DRAR-CPI). After screening of disease targets of liver fibrosis by Gene Cards database, the protein-protein interaction was analyzed with use of STRING database, and GO(gene ontology) analysis and KEGG(Kyoto encyclopedia of genes and genomes) enrich analysis were also carried out. Moreover, an iTRAQ proteomics technology was used to determine protein expression in liver tissues of rats in TFL, model and blank groups to verify the targets. Furthermore, Cytoscape software was used to establish and visualize the network of chemical components, targets and pathways, and predict the potential Q-marker of TFL. The results showed that the levels of TBiL, DBiL, IBiL, ALT, and AST in the model group were significantly higher than those in the blank normal group(P<0.05), and the above levels in the treatment groups were lower than those in the model group, but with no significant differences. Masson staining showed that the liver damage and the degree of fibrosis were severe in the model group, and were relieved to different degrees in the treatment groups. Then, 74 chemical components were screened, which could act on 865 targets such as EGFR and SRC, participating in the regulation of cancer pathways, PI3 K-Akt signaling pathway, HIF-1 signaling pathway and other signaling pathways closely related to liver fibrosis. Pinocembrin, quercetin, epicatechin, procyanidin A2, naringenin, nobiletin, phlorizin and rutin showed the highest correlation with liver fibrosis-related targets and pathways. Proteomics results showed that a total of 18 proteins among the 45 proteins predicted by internet pharmacology were identified, among which 6 proteins were significantly expressed, including 5 up-regulated proteins and 1 down-regulated protein. The protein expression of ALB, PLG, HSP90 AA1, EGFR and MAP2 K1 was significantly returned to a normal state in the TFL treatment groups. In conclusion, TFL may demonstrate the anti-hepatic fibrosis and potential hepatoprotective effects by regulating the expression of ALB, PLG, HSP90 AA1, EGFR and MAP2 K1, which may be associated with the regulation of multiple signaling pathways related to liver fibrosis such as PI3 K-Akt pathway. Pinocembrin, quercetin, epicatechin, procyanidin A2, naringenin, nobiletin, phlorizin and rutin could be regarded as potential Q-markers of TFL for quality control.

Association between toll-like receptors 9 (TLR9) gene polymorphism and risk of pulmonary tuberculosis: meta-analysis.

BACKGROUND: Previous studies indicated that the single nucleotide polymorphisms (SNPs) in TLR9 gene might be associated with Tuberculosis (TB) risk. However, the results are inconsistent and inconclusive. METHODS: 1745 articles from four databases were involved in our study. A meta-analysis on the associations between the seven polymorphisms and TB risk was carried out by comparison using different genetic models. RESULTS: In this systematic review 8 studies from seven English articles were analyzed. Our results showed that rs352139 is significantly associated with TB risk (AA vs. AG, OR 0.77, 95% CI 0.65-0.92, P = 0.004). In the ethnic subgroup analysis, Indonesians with AA genotype had a decreased susceptibility while Mexicans with GG allele had an increased risk. CONCLUSIONS: The meta-analysis indicated that rs352139 polymorphism might be associated with decreased TB risk in Indonesians whereas increased risk in Mexicans. Whether the observed association was due to causal effect needs to be further studied.

The advances in adjuvant therapy for tuberculosis with immunoregulatory compounds.

Tuberculosis (TB) is a chronic bacterial disease, as well as a complex immune disease. The occurrence, development, and prognosis of TB are not only related to the pathogenicity of Mycobacterium tuberculosis (Mtb), but also related to the patient's own immune state. The research and development of immunotherapy drugs can effectively regulate the body's anti-TB immune responses, inhibit or eliminate Mtb, alleviate pathological damage, and facilitate rehabilitation. This paper reviews the research progress of immunotherapeutic compounds for TB, including immunoregulatory compounds and repurposing drugs, and points out the existing problems and future research directions, which lays the foundation for studying new agents for host-directed therapies of TB.

Preparation of Calcium-Binding Peptides Derived from Mackerel (Scomber japonicus) Protein and Structural Characterization and Stability Analysis of Its Calcium Complexes.

The purpose of this study was to prepare mackerel peptides (MPs) with calcium-binding capacity through an enzyme method and to investigate the potential role they play in improving the bioavailability of calcium in vitro. The calcium-binding capacity, degree of hydrolysis (DH), molecular weight (MW), and charge distribution changes with the enzymolysis time of MPs were measured. The structural characterization of mackerel peptide-calcium (MP-calcium) complexes was performed using spectroscopy and morphology analysis. The results showed that the maximum calcium-binding capacity of the obtained MPs was 120.95 mg/g when alcalase was used for 3 h, with a DH of 15.45%. Moreover, with an increase in hydrolysis time, the MW of the MPs decreased, and the negative charge increased. The carboxyl and amino groups in aspartic (Asp) and glutamate (Glu) of the MPs may act as calcium-binding sites, which are further assembled into compact nanoscale spherical complexes with calcium ions through intermolecular interactions. Furthermore, even under the influence of oxalic acid, MP-calcium complexes maintained a certain solubility. This study provides a basis for developing new calcium supplements and efficiently utilizing the mackerel protein resource.

Multi-cohort analysis reveals immune subtypes and predictive biomarkers in tuberculosis.

Tuberculosis (TB) remains a significant global health threat, necessitating effective strategies for diagnosis, prognosis, and treatment. This study employs a multi-cohort analysis approach to unravel the immune microenvironment of TB and delineate distinct subtypes within pulmonary TB (PTB) patients. Leveraging functional gene expression signatures (Fges), we identified three PTB subtypes (C1, C2, and C3) characterized by differential immune-inflammatory activity. These subtypes exhibited unique molecular features, functional disparities, and cell infiltration patterns, suggesting varying disease trajectories and treatment responses. A neural network model was developed to predict PTB progression based on a set of biomarker genes, achieving promising accuracy. Notably, despite both genders being affected by PTB, females exhibited a relatively higher risk of deterioration. Additionally, single-cell analysis provided insights into enhanced major histocompatibility complex (MHC) signaling in the rapid clearance of early pathogens in the C3 subgroup. This comprehensive approach offers valuable insights into PTB pathogenesis, facilitating personalized treatment strategies and precision medicine interventions.

The changes and its significance of peripheral blood NK cells in patients with tuberculous meningitis.

Objective: Tuberculous meningitis (TBM) is the most severe form of tuberculosis (TB). The purpose of this study was to explore the relationship between the number of natural killer (NK) cells and adaptive immune status, and disease severity in TBM patients. Methods: We conducted a retrospective study on 244 TB patients and 146 healthy control subjects in the 8th Medical Center of the PLA General Hospital from March 2018 and August 2023. Results: The absolute count of NK cells in the peripheral blood of TBM patients was significantly lower than that in normal controls (NC), latent tuberculosis infection (LTBI), and non-severe TB (NSTB) patients (p < 0.05). The proportion of TBM patients (48.7%) with a lower absolute count of NK cells than the normal reference value was significantly higher than that in NC (5.2%) and LTBI groups (4.0%) (p < 0.05), and slightly higher than that in NSTB group (36.0%) (p > 0.05). The absolute counts of lymphocyte subsets in TBM combined with other active TB group, etiology (+) group, IGRA (-) group, and antibody (+) group were lower than that in simple TBM group, etiology (-) group, IGRA (+) group, and antibody (-) group, respectively. The CD3+ T, NK, and B cells in BMRC-stage III TBM patients were significantly lower than those in stage I and stage II patients (p < 0.05). The counts of CD3+ T, CD4+ T, and B cells in the etiology (+) group were significantly lower than those in the etiology (-) group (p < 0.05). Conclusion: The absolute counts of lymphocyte subsets in the peripheral blood of TBM patients were significantly decreased, especially in NK cells. The reduction of these immune cells was closely related to the disease severity and had a certain correlation with cellular and humoral immune responses. This study helps to better understand the immune mechanism of TBM and provides reliable indicators for evaluating the immune status of TBM patients in clinical practice.

Evaluation of droplet digital polymerase chain reaction by detecting cell-free deoxyribonucleic acid in pleural effusion for the diagnosis of tuberculous pleurisy: a multicentre cohort study.

OBJECTIVES: Tuberculous pleurisy is one of the most common types of extra-pulmonary tuberculosis, but the sensitivity of conventional mycobacterial culture (Culture) or Xpert MTB/RIF assay (Xpert) is not satisfying. This multicentre cohort study evaluated the accuracy of a new cell-free DNA droplet digital PCR assay (cf-ddPCR) for diagnosing tuberculous pleurisy. METHODS: Patients with suspected tuberculosis (≥5 years of age) with pleural effusion were consecutively recruited from nine research sites across six provinces in China between September 2020 to May 2022. Culture, Xpert, Xpert MTB/RIF Ultra assay (Ultra), real-time PCR, and cf-ddPCR were performed simultaneously for all specimens. RESULTS: A total of 321 participants were enrolled, and data from 281 (87.5%) participants were available, including 105 definite tuberculous pleurisy, 113 possible tuberculous pleurisy and 63 non-tuberculous pleurisy according to the composite reference standard. The sensitivity of cf-ddPCR was 90.5% (95/105, 95% CI, 82.8-95.1%) in the definite tuberculous pleurisy group, which was significantly higher than those of Culture (57.1%, 60/105, 95% CI, 47.1-66.6%, p < 0.001), Xpert (46.7%, 49/105, 95% CI, 37.0-56.6%, p < 0.001), Ultra (69.5%, 73/105, 95% CI, 59.7-77.9%, p < 0.001) and real-time PCR (75.2%, 79/105, 95% CI, 65.7-82.9%, p < 0.001). In possible tuberculous pleurisy, whose results of Culture and Xpert were both negative, the sensitivity of cf-ddPCR was 61.1% (69/113, 95% CI, 51.4-70.0%), which was still significantly higher than that of Ultra (27.4%, 31/113, 95% CI, 19.7-36.8%, p < 0.001) and real-time PCR (38.9%, 44/113, 95% CI, 30.0-48.6%, p < 0.001). DISCUSSION: The performance of cf-ddPCR is superior to Culture, Xpert, Ultra, and real-time PCR, indicating that improved diagnostic accuracy can be anticipated by incorporating this new assay.

[Optimization of preparation technology of LIUWEI cataplasm, a kind of Zhuang national herbs].

OBJECTIVE: To optimize preparation process of liuwei cataplasm, a Zhuang folk medical herb popularly applied as a kind of rheumatism, rheumatoid drug in Guangxi Zhuang Autonomous Region. METHODS: Orthogonal design test was employed to optimise matrix proportion and molding technology of liuwei cataplasma with glossiness, adhesive power, matrix residue, skin following and repeatedly exposing as indexes. RESULTS: Optimum matrix ratio of PANA, pressure sensitive adhesive, CNC-Na, gelatin, dihydroxyaluminium aminoacetate and glycerol was 0.5:1.0:0.4:0.1:0.3:3.0. Optimized parameters of technology were as follows: stiring speed 600 r/min, refining temperature 60 degrees C and drug loading of Liuwei extract 13.04%. CONCLUSION: Optimized liuwei cataplasm has a good adhesive power, exipcients and glossiness, meanwhile drug loading is large and no skin residue. The process is simple, stable and viable.

[Pharmacokinetics and bioavailability of ginsenoside Rg1 in rats].

OBJECTIVE: To investigate the pharmacokinetics and bioavailability of ginsenoside Rg1 in rats. METHODS: Ginsenoside Rg1 was oral administered or intravenous administered to each rat. The plasma concentration of ginsenoside Rg1 was estimated by RP-HPLC. 3P97 software was used to calculate pharmacokinetic parameters. RESULTS: Main parameters of ginsenoside Rg1 after oral or intravenous administered were: AUC(0 --> t), 322.70 +/- 20.78, 99.76 +/- 8.91 microg x h/mL, CL 0.08 +/- 0.02, 3.01 +/- 0.69 L/(kg x h), V 0.23 +/- 0.01, 22.75 +/- 2.09 L/kg, t1/2alpha 0.48 +/- 0.18, 0.87 +/- 0.21 h, t1/2beta 19.57 +/- 2.81, 18.68 +/- 2.74 h, MRT6.91 +/- 0.99, 8.15 +/- 1.05 h(-1), respectively. The relative oral bioavailability of ginsenoside Rg1 was 2.5%. CONCLUSION: The oral bioavailability of ginsenoside Rg1 is very low.

In vitro activities of contezolid (MRX-I) against drug-sensitive and drug-resistant Mycobacterium tuberculosis.

A novel oxazolidinone for the treatment of Mycobacterium tuberculosis has been developed, but the activity of contezolid (MRX-I) still needs to be clarified. In this study, we isolated Mycobacterium tuberculosis from 48 clinical patients with pulmonary tuberculosis. Roche drug susceptibility tests identified drug-sensitive and 39 drug-resistant M. tuberculosis isolates. Drug susceptibility assays indicated that MRX-I exhibited anti-Mycobacterium tuberculosis activity against both drug-sensitive and drug-resistant isolates, with an advantage against drug-resistant isolates. The results also showed that the anti-Mycobacterium tuberculosis activity was comparable to that of linezolid. IMPORTANCE Currently, Mycobacterium tuberculosis has exhibited increased drug resistance, leading to ineffective drug treatment in many patients with tuberculosis. Among the anti-Mycobacterium tuberculosis drugs, oxazolidinones have been gradually developed. Contezolid (MRX-I) has been newly developed in China with advantages versus the first oxazolidinone antibiotic approved by the Food and Drug Administration for clinical use, but the anti-M. tuberculosis activity needs to be further clarified. In this study, in vitro activities of MRX-I against M. tuberculosis were tested. The drug susceptibility assays indicated that MRX-I exhibited anti-M. tuberculosis activity comparable to that of linezolid, with an advantage against drug-resistant isolates.

Clinical characteristics of patients with non-tuberculous mycobacterial pulmonary disease: a seven-year follow-up study conducted in a certain tertiary hospital in Beijing.

Background: The incidence of non-tuberculous mycobacterial pulmonary disease (NTM-PD) has increased in recent years. However, the clinical and immunologic characteristics of NTM-PD patients have received little attention. Methods: NTM strains, clinical symptoms, underlying diseases, lung CT findings, lymphocyte subsets, and drug susceptibility tests (DSTs) of NTM-PD patients were investigated. Then, the counts of immune cells of NTM-PD patients and their correlation were evaluated using principal component analysis (PCA) and correlation analysis. Results: 135 NTM-PD patients and 30 healthy controls (HCs) were enrolled from 2015 to 2021 in a certain tertiary hospital in Beijing. The number of NTM-PD patients increased every year, and Mycobacterium intracellulare (M. intracellulare), M. abscessus, M. avium, and M. kansasii were the major pathogens of NTM-PD. The main clinical symptoms of NTM-PD patients were cough and sputum production, and the primary lung CT findings were thin-walled cavity, bronchiectasis, and nodules. In addition, we identified 23 clinical isolates from 87 NTM-PD patients with strain records. The DST showed that almost all of M. abscessus and M. avium and more than half of the M. intracellulare and M. avium complex groups were resistant to anti-tuberculosis drugs tested in this study. M. xenopi was resistant to all aminoglycosides. M. kansasii was 100% resistant to kanamycin, capreomycin, amikacin, and para-aminosalicylic acid, and sensitive to streptomycin, ethambutol, levofloxacin, azithromycin, and rifamycin. Compared to other drugs, low resistance to rifabutin and azithromycin was observed among NTM-PD isolates. Furthermore, the absolute counts of innate and adaptive immune cells in NTM-PD patients were significantly lower than those in HCs. PCA and correlation analysis revealed that total T, CD4+, and CD8+ T lymphocytes played an essential role in the protective immunity of NTM-PD patients, and there was a robust positive correlation between them. Conclusion: The incidence of NTM-PD increased annually in Beijing. Individuals with bronchiectasis and COPD have been shown to be highly susceptible to NTM-PD. NTM-PD patients is characterized by compromised immune function, non-specific clinical symptoms, high drug resistance, thin-walled cavity damage on imaging, as well as significantly reduced numbers of both innate and adaptive immune cells.

LTBI-negative close contacts of tuberculosis are more likely to develop the disease: enlightenment and lessons from a cluster outbreak.

Background: Tuberculosis (TB) prevention and control among groups living together, such as students, workers, older adults in nursing homes, and prisoners, present many challenges due to their particular age and environmental factors, which can make them more susceptible to TB clusters with significant societal impact. This study aimed to evaluate a TB cluster outbreak epidemic in a university and provide suggestions for improving TB control strategies for groups living together. Methods: Pulmonary TB screening and close-contact investigation were conducted using acid-fast staining, sputum culture, GeneXpert testing, tuberculin skin testing (TST), interferon-gamma release assay (IGRA), and chest computed tomography (CT). GraphPad Prism 9.5.1 was utilized for data analysis. Collected epidemic data were comprehensively analyzed by rate comparison. Results: The TB cluster outbreak epidemic was identified with an index case confirmed positive. The initial screening was conducted on potential close contacts of the index case, and the TST's positive rate (diameter ≥ 5 mm) and strong positive rate (diameter ≥ 15 mm) among these close contacts were 65.60% (21/32) and 34.40% (11/32), respectively. Moreover, the latent TB infection (LTBI) rate (diameter ≥ 10 mm) was 43.75% (14/32), and the IGRA's positive rate was 9.30% (3/32). Chest CT scans did not reveal any abnormalities. Surprisingly, 5 of the close contacts developed active TB in the second screening, accompanied by changes from negative to positive TST and/or IGRA results, after 3 months of follow-up. Accordingly, we expanded the screening scope to include another 28 general contacts. We found that the positive rate (78.00%, 25/32), strong positive rate (50.00%, 16/32), and LTBI rate (62.50%, 20/32) of the 32 close contacts were significantly higher than those of the additional general contacts (28.00%, 8/28; 14.3%, 4/28; 25.00%, 7/28), as indicated by p < 0.05. Conclusion: In the event of an epidemic TB outbreak, it is essential to rapidly identify the source of infection and initiate timely screening of close contacts. The initial screening should be focused on individuals without LTBI, who are at higher risk of developing TB. In purified protein derivative-negative individuals living in groups, additional vaccination or revaccination with Bacille Calmette-Guérin may help prevent cluster outbreaks of TB.

Effects of combined treatment of electrolytic water and chitosan on the quality and proteome of large yellow croaker (Pseudosciaena crocea) during refrigerated storage.

The labeled quantitative proteomic method was used to study the changes in muscle proteins of large yellow croaker (Pseudosciaena crocea) treated with electrolytic water (EW) and chitosan (CHI) combined preservation during 12 days of refrigeration storage (4 °C). The analysis indicated that the freshness instructed by total viable count (TVC), total volatile basic nitrogen (TVB-N) and K value was significantly maintained after combined preservation during storage at 4 °C for 12 days (CS12). Furthermore, 46 differentially abundant proteins (DAPs) were detected in storage at 4 °C for 12 days (S12) compared to the freshness group (F), which bioinformatics confirmed were mainly skeletal proteins and enzymes. Correlation analysis showed that 19 highly correlated DAPs could be used as potential protein markers of freshness. Changes in the relation of freshness and protein were shown in further correlative analysis of F and CS12, which were caused by combined preservation. Therefore, combined preservation is promising in the quality and stability of large yellow croakers.