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Background Gut microbiota plays a critical role in many important physiological processes and is linked with various pulmonary infectious diseases. The relationship between pulmonary tuberculosis (PTB) and gut microbiota has been poorly studied. The present study aimed to characterize gut microbiota in pediatric patients with PTB. Methods A case-controlled study was executed for the characterization of gut microbiota in pediatric PTB patients. Fecal samples were collected from the PTB patients and healthy controls upon admission. In addition, a one-month follow-up assessment was performed to investigate alterations in the gut microbiota post anti-tuberculosis treatment. 16SrDNA sequencing analysis of fecal DNA was completed on the Illumina MiSeq platform. Results Compared with healthy controls, the gut microbiota of pediatric patients with PTB was characterized by decreased microbial diversity. PTB patients further presented an up-regulation of the pro-inflammatory bacteria Prevotella, the opportunistic pathogen Enterococcus, as well as a reduction of beneficial bacteria including Ruminococcaceae , Bifidobacteriaceae and prausnitzii. One-month after anti-tuberculosis therapy, the richness of gut microbiota in PTB patients was distinctly depleted. Conclusions The gut microbiota of pediatric patients with PTB was significantly distinct from healthy controls. Additionally, the richness of gut microbiota in PTB patients decreased after one-month anti-tuberculosis treatment. It is hypothesized that the homeostasis of gut microbiota in PTB patients may affect the pathogenies of PTB by de-regulation of the hosts’ immune status through the gut-lung axis.

The objective of this study is to evaluate users’ perceptions and preferences on the design features of the COVID-19 prevention promotion icon from the perspective of users’ aesthetic and perceptual needs. In this study, 120 officially published icons from 24 countries and regions were collected from online platforms for ranking tests, and then the top-ranked icons were subjectively rated by the semantic differential method. By evaluating the quality of users’ perceptions of multiple semantic dimensions of icons, we extracted the perceptual semantic words that users valued as the main icon design features. Spearmen correlations were applied to derive possible correlations between user rankings and semantic scales, and a Friedman test was also conducted to determine the true differences in user perceptions and preferences for different styles of icons. Factor analysis was conducted to extract six perceptual words that influence the design features of the COVID-19 prevention promotion icon. The methodology adopted in this study facilitated the screening of design features related to icon effectiveness, and the findings show that “Interesting,” “Simple,” “Familiar, “Recognizable,” “Concrete,” and “Close(semantic distance)” are the key features that influence users’ perception and preference of COVID-19 icon design. The results of this study can be used as the basis for designing and improving publicity icons for preventive measures in COVID-19, and the methods adopted in this study can be applied to evaluate other types of icon design.

Background Matrix metalloproteinase-7 (MMP-7) has emerged as a promising biomarker for the early detection of biliary atresia (BA), with potential to significantly improve diagnostic accuracy and patient outcomes. This meta-analysis evaluated the diagnostic performance of MMP-7 to determine its clinical utility in the identification of BA. Methods A comprehensive literature search was performed in PubMed, Embase, Web of Science, and the Cochrane Library for studies published through March 21, 2024. Study quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. Diagnostic parameters including sensitivity, specificity, likelihood ratios, and diagnostic odds ratios were pooled. Summary receiver operating characteristic curves were constructed to evaluate overall diagnostic performance. Results 9 studies comprising 710 patients were included in the analysis. MMP-7 demonstrated a pooled sensitivity of 0.80 (95% CI: 0.58–0.92) and specificity of 0.97 (95% CI: 0.90–0.99), with an area under the curve of 0.97 (95% CI: 0.95–0.98). Subgroup analyses by geographic sample size, study type and mean/median age revealed no significant differences in diagnostic performance. An inverse relationship was observed between cutoff values and sensitivity, with higher thresholds yielding lower sensitivity but improved specificity. Conclusion The sensitivity of MMP-7 is influenced by sample processing methods, sample handling time, and substantial variability in cutoff values. Therefore, it cannot serve as an independent diagnostic tool for BA, and BA diagnosis should continue to rely on the gold standard. However, MMP-7 may serve as a valuable tool for risk stratification in BA. Future research should investigate the diagnostic performance of MMP-7 across varying cutoff values, reflecting the observed variability across studies. PROSPERO registration number CRD42024532998.

Lotus seed embryos, a key component in traditional Chinese medicine, have attracted growing scientific interest due to their wide-ranging therapeutic potential. Among the bioactive compounds found in lotus seed embryos, three bisbenzylisoquinoline alkaloids—liensinine, isoliensinine, and neferine—stand out for their diverse pharmacological activities. These alkaloids are known to exhibit significant antitumor, anti-inflammatory, antihypertensive, neuroprotective, and antifibrotic effects, which make them promising candidates for the treatment of various chronic and acute diseases. Recent studies have highlighted their ability to modulate key signaling pathways involved in cancer progression, inflammation, fibrosis, and neurodegeneration. The precise mechanisms underlying their actions include modulation of oxidative stress, inhibition of pro-inflammatory cytokines, regulation of apoptosis, and modulation of cellular metabolism. This review aims to provide an in-depth overview of the pharmacological relevance of these alkaloids, focusing on their mechanisms of action and their therapeutic potential across different disease models. By synthesizing current evidence from preclinical studies, this review also lays a solid scientific foundation for future research, supporting the rational design and development of lotus-derived compounds for clinical application.

Ion channels regulate ion transport across cell or organelle membranes, playing an important role in various biological processes. Sodium channel Nav1.4 is critical to initiating and propagating action potentials in skeletal muscles, and its dysfunction is associated with a variety of diseases, such as non-dystrophic myotonias. In this study, U-actitoxin-Avd3i (Avd3i), a Kunitz-type toxin derived from Anemonia viridis, was expressed in prokaryotic systems and was subsequently purified via high-pressure liquid chromatography. Patch clamp recording showed that Avd3i inhibited Nav1.4 in a concentration-dependent manner, with an IC50 of 25.43 μM. However, the toxin exerted no inhibitory activity in Nav1.5/Nav1.7 channels or Kv1.1/Kv1.3/Kv1.4/Kv4.2 potassium channels. Our study found that the sea anemone-derived toxin Avd3i inhibited sodium channel Nav1.4, providing a novel molecule that can act on the channel.

Intrathyroid thymic carcinoma (ITC) is a rare malignant tumour. We present nine cases of ITC that were analysed by immunohistochemical staining, of which five were analysed using whole exome sequencing (WES). These cases included six women and three men with an age range of 31–66 years. The average postoperative follow-up term was 37.8 months (range, 7–95 months), and all patients survived well except for one case with lung metastasis. Microscopically, ITC showed solid islands of tumour cells separated by fibrous connective tissue containing lymphocytes and other inflammatory cells. Tumour cells strongly expressed Ckpan (AE1/AE3), P63, and CD117. And all cases but one were positive for CD5. The median value of Ki-67 was 32% (range 10–60%). We observed partial positivity of Syn and CgA in only one case. ITC shares morphological and immunohistochemical similarities with thymic squamous cell carcinoma. In situ hybridization of EBER showed negative results. All cases were microsatellite stable, and the tumour mutational burden of the 5 cases was all < 1 mutations/Mb. WES showed higher mutation rates for N4BP1 (2/5), and many genetic alterations were related to the NF-kB signalling pathway, which is crucial for insight into the molecular mechanisms of the occurrence and development of ITC.

Adenoid cystic carcinoma (AdCC) of the breast is a rare indolent carcinoma of salivary gland-type tumors, frequently associated with MYB genetic alteration. Solid and basaloid adenoid cystic carcinoma (SB-AdCC) is considered a sparse variant of AdCC. This study sought to search for clinicopathological and genomic features in SB-AdCC. Registered clinicopathological data on a cohort of 13 AdCC of the breast cases, including six conventional adenoid cystic carcinoma (C-AdCC) cases and seven SB-AdCC cases, were collected. MYB gene rearrangement via fluorescent in situ hybridization was investigated and MYB protein expression was evaluated by immunohistochemistry. Compared with C-AdCC, we found that the distribution of SB-AdCC cases were shifted to older age and were more frequently distant metastasis. Moreover, metastasis cases also showed a high (exceed 30%) Ki-67 index. Both groups showed MYB rearrangements and MYB protein expression, but they were less frequent in SB-AdCC than C-AdCC. To conclude, our results suggest that SB-AdCC is an aggressive variant of mammary AdCC with a higher incidence of distant metastases compared with C-AdCC, though they share common molecular features. A high Ki-67 index may be an adverse prognostic factor for metastasis.

Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease characterized by the fibrotic thickening of the alveolar walls, resulting in compromised gas exchange, restricted ventilation, and respiratory failure. It has been indicated that elastase inhibitors reduced the severity of IPF by neutralizing excessive elastase levels in the lungs. ShSPI is an elastase inhibitor derived from centipede toxin. The present study evaluates the therapeutic effects of ShSPI in a bleomycin-induced idiopathic pulmonary fibrosis model. According to the results, ShSPI markedly reduced the weight loss, showing the improvement of health status in bleomycin-induced mice. Its robust antifibrotic effects were evidenced by the mitigation of alveolar structural damage, reduction in inflammatory cell infiltration, inhibition of collagen deposition, and suppression of fibrotic nodule formation. ShSPI effectively attenuated inflammatory responses by downregulating pro-inflammatory factors (IL-6, IL-1β, and MCP-1) and upregulating the anti-inflammatory factor interleukin-10 (IL-10). After delivered via inhalation, ShSPI exhibited favorable pharmacokinetic properties. It could be detected at 8 h at doses of 1 mg/kg and achieved maximum plasma concentrations (Cmax) of 188.00 ± 64.40 ng/mL in vivo. At high doses (160 mg/kg), ShSPI maintained a strong safety profile, with no detectable toxicity observed. This feature shows the therapeutic potential of ShSPI in the treatment of idiopathic pulmonary fibrosis and provides valuable evidence for its development as a novel peptide-based therapy.

Background The first-line anti-tuberculosis (anti-TB) drugs require long-term administration, and their plasma concentrations are closely associated with therapeutic efficacy and safety. The primary objective of this study was to analyze interindividual and interdrug variability in plasma concentrations of first-line anti-TB drugs in pediatric patients and to investigate factors influencing drug concentrations. Methods A retrospective analysis was conducted on 110 pediatric tuberculosis (TB) patients who underwent therapeutic drug monitoring (TDM) for anti-TB drugs between January 2022 and November 2023. Patients with complete TDM data were included, defined as those receiving the tablet formulation at doses consistent with the 2010 World Health Organization recommendations, with blood samples collected 5–7 days after drug administration. Accordingly, TDM data were analyzed for isoniazid (INH, n  = 105), rifampicin (RFP, n  = 83), and pyrazinamide (PZA, n  = 103). Results Two hours after administration, the proportions of children with plasma concentrations below the target range were 31.4% (33/105) for INH, 30.1% (25/83) for RFP, and 3.9% (4/103) for PZA. Multivariate logistic regression analysis revealed that higher doses (mg/kg) were significantly associated with achieving a therapeutic plasma concentration ( P  < 0.05). Conclusion Subtherapeutic plasma concentrations of RFP and INH are common in pediatric TB patients receiving guideline-recommended doses of first-line anti-tuberculosis drugs. The administered dose (mg/kg) significantly influences plasma drug concentrations, underscoring the necessity of TDM for first-line anti-tuberculosis drugs in children and individualized treatment plan adjustments to optimize TB management. Clinical trial Not applicable.