Objective To explore the diagnostic value of exhaled volatile organic compounds (VOCs) for cystic fibrosis (CF). Methods A systematic search was conducted in PubMed, EMbase, Web of Science, Cochrane Library, CNKI, Wanfang, VIP, and SinoMed databases up to August 7, 2024. Studies that met the inclusion criteria were selected for data extraction and quality assessment. The quality of included studies was assessed by the Newcastle-Ottawa Scale (NOS), and the risk of bias and applicability of included prediction model studies were assessed by the prediction model risk of bias assessment tool (PROBAST). Results A total of 10 studies were included, among which 5 studies only identified specific exhaled VOCs in CF patients, and another 5 developed 7 CF risk prediction models based on the identification of VOCs in CF. The included studies reported a total of 75 exhaled VOCs, most of which belonged to the categories of acylcarnitines, aldehydes, acids, and esters. Most models (n=6, 85.7%) only included exhaled VOCs as predictive factors, and only one model included factors other than VOCs, including forced expiratory flow at 75% of forced vital capacity (FEF75) and modified Medical Research Council scale for the assessment of dyspnea (mMRC). The accuracy of the models ranged from 77% to 100%, and the area under the receiver operating characteristic curve ranged from 0.771 to 0.988. None of the included studies provided information on the calibration of the models. The results of the Prediction Model Risk of Bias Assessment Tool (PROBAST) showed that the overall bias risk of all predictive model studies was high, and the overall applicability was unclear. Conclusion The exhaled VOCs reported in the included studies showed significant heterogeneity, and more research is needed to explore specific compounds for CF. In addition, risk prediction models based on exhaled VOCs have certain value in the diagnosis of CF, but the overall bias risk is relatively high and needs further optimization from aspects such as model construction and validation.

Oral solid dosage forms require processes such as disintegration and dissolution to release the drug before it can be absorbed and utilized by the body. In this manuscript, imaging technology was used to continuously visualize and characterize the in vitro static drug release process of gliclazide modified release tablets from 15 manufacturers, combined with the traditional method of in vitro dissolution testing, to determine the release profile of gliclazide modified release tablets, to evaluate the similarity of the release profiles by using the similarity factor (f₂) method and based on the analysis of the release profiles fitted with a variety of mathematical models. The results indicate that the gliclazide modified release tablets produced by 14 companies are hydrophilic gel matrix tablets. Compared to the reference listed drug, the release profiles of formulations from 11 companies show high similarity (f₂ > 50) to the reference. Among these, formulations with visual characteristics similar to the reference exhibit similar release curves. This study provides an alternative method for the in vitro consistency evaluation of gliclazide modified release tablets, aiming to assess the in vitro release behaviour of generic formulations more accurately and comprehensively.

ObjectiveNeuroinflammation plays a crucial role in both the onset and progression of ischemic stroke, exerting a significant impact on the recovery of the central nervous system. Excessive neuroinflammation can lead to secondary neuronal damage, further exacerbating brain injury and impairing functional recovery. As a result, effectively modulating and reducing neuroinflammation in the brain has become a key therapeutic strategy for improving outcomes in ischemic stroke patients. Among various approaches, targeting immune regulation to control inflammation has gained increasing attention. This study aims to investigate the role of in vitro induced regulatory T cells (Treg cells) in suppressing neuroinflammation after ischemic stroke, as well as their potential therapeutic effects. By exploring the mechanisms through which Tregs exert their immunomodulatory functions, this research is expected to provide new insights into stroke treatment strategies. MethodsNaive CD4⁺ T cells were isolated from mouse spleens using a negative selection method to ensure high purity, and then they were induced in vitro to differentiate into Treg cells by adding specific cytokines. The anti-inflammatory effects and therapeutic potential of Treg cells transplantation in a mouse model of ischemic stroke was evaluated. In the middle cerebral artery occlusion (MCAO) model, after Treg cells transplantation, their ability to successfully migrate to the infarcted brain region and their impact on neuroinflammation levels were examined. To further investigate the role of Treg cells in stroke recovery, the changes in cytokine expression and their effects on immune cell interactions was analyzed. Additionally, infarct size and behavioral scores were measured to assess the neuroprotective effects of Treg cells. By integrating multiple indicators, the comprehensive evaluation of potential benefits of Treg cells in the treatment of ischemic stroke was performed. ResultsTreg cells significantly regulated the expression levels of both pro-inflammatory and anti-inflammatory cytokines in vitro and in vivo, effectively balancing the immune response and suppressing excessive inflammation. Additionally, Treg cells inhibited the activation and activity of inflammatory cells, thereby reducing neuroinflammation. In the MCAO mouse model, Treg cells were observed to accumulate in the infarcted brain region, where they significantly reduced the infarct size, demonstrating their neuroprotective effects. Furthermore, Treg cell therapy notably improved behavioral scores, suggesting its role in promoting functional recovery, and increased the survival rate of ischemic stroke mice, highlighting its potential as a promising therapeutic strategy for stroke treatment. ConclusionIn vitro induced Treg cells can effectively suppress neuroinflammation caused by ischemic stroke, demonstrating promising clinical application potential. By regulating the balance between pro-inflammatory and anti-inflammatory cytokines, Treg cells can inhibit immune responses in the nervous system, thereby reducing neuronal damage. Additionally, they can modulate the immune microenvironment, suppress the activation of inflammatory cells, and promote tissue repair. The therapeutic effects of Treg cells also include enhancing post-stroke recovery, improving behavioral outcomes, and increasing the survival rate of ischemic stroke mice. With their ability to suppress neuroinflammation, Treg cell therapy provides a novel and effective strategy for the treatment of ischemic stroke, offering broad application prospects in clinical immunotherapy and regenerative medicine.

The human oral microbiome harbors one of the most diverse microbial communities in the human body, playing critical roles in oral and systemic health. Recent technological innovations are propelling the characterization and manipulation of oral microbiota. High-throughput sequencing enables comprehensive taxonomic and functional profiling of oral microbiomes. New long-read platforms improve genome assembly from complex samples. Single-cell genomics provides insights into uncultured taxa. Advanced imaging modalities including fluorescence, mass spectrometry, and Raman spectroscopy have enabled the visualization of the spatial organization and interactions of oral microbes with increasing resolution. Fluorescence techniques link phylogenetic identity with localization. Mass spectrometry imaging reveals metabolic niches and activities while Raman spectroscopy generates rapid biomolecular fingerprints for classification. Culturomics facilitates the isolation and cultivation of novel fastidious oral taxa using high-throughput approaches. Ongoing integration of these technologies holds the promise of transforming our understanding of oral microbiome assembly, gene expression, metabolites, microenvironments, virulence mechanisms, and microbe-host interfaces in the context of health and disease. However, significant knowledge gaps persist regarding community origins, developmental trajectories, homeostasis versus dysbiosis triggers, functional biomarkers, and strategies to deliberately reshape the oral microbiome for therapeutic benefit. The convergence of sequencing, imaging, cultureomics, synthetic systems, and biomimetic models will provide unprecedented insights into the oral microbiome and offer opportunities to predict, prevent, diagnose, and treat associated oral diseases.
Humans ; Phylogeny ; Biomimetics ; Dysbiosis ; Homeostasis ; Mass Spectrometry

Recent clinical studies have shown that mutation of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) gene in cancer cells may be associated with immunosuppressive tumor microenvironment (TME) and poor response to immune checkpoint blockade (ICB) therapy. Therefore, efficiently restoring PTEN gene expression in cancer cells is critical to improving the responding rate to ICB therapy. Here, we screened an adeno-associated virus (AAV) capsid for efficient PTEN gene delivery into B16F10 tumor cells. We demonstrated that intratumorally injected AAV6-PTEN successfully restored the tumor cell PTEN gene expression and effectively inhibited tumor progression by inducing tumor cell immunogenic cell death (ICD) and increasing immune cell infiltration. Moreover, we developed an anti-PD-1 loaded phospholipid-based phase separation gel (PPSG), which formed an in situ depot and sustainably release anti-PD-1 drugs within 42 days in vivo. In order to effectively inhibit the recurrence of melanoma, we further applied a triple therapy based on AAV6-PTEN, PPSG^@anti-PD-1 and CpG, and showed that this triple therapy strategy enhanced the synergistic antitumor immune effect and also induced robust immune memory, which completely rejected tumor recurrence. We anticipate that this triple therapy could be used as a new tumor combination therapy with stronger immune activation capacity and tumor inhibition efficacy.

A major challenge facing photodynamic therapy (PDT) is that the activity of the immune-induced infiltrating CD8⁺ T cells is subject to the regulatory T lymphocytes (Tregs), leaving the tumor at risk of recurrence and metastasis after the initial ablation. To augment the antitumor response and reprogram the immunosuppressive tumor microenvironment (TME), a supramolecular photodynamic nanoparticle (DACss) is constructed by the host-guest interaction between demethylcantharidin-conjugated β-cyclodextrin (DMC-CD) and amantadine-terminated disulfide-conjugated FFVLGGGC peptide with chlorin e6 decoration (Ad-ss-pep-Ce6) to achieve intelligent delivery of photosensitizer and immunomodulator for breast cancer treatment. The acid-labile β-carboxamide bond of DMC-CD is hydrolyzed in response to the acidic TME, resulting in the localized release of DMC and subsequent inhibition of Tregs. The guest molecule Ad-ss-pep-Ce6 can be cleaved by a high level of intracellular GSH, reducing photosensitizer toxicity and increasing photosensitizer retention in the tumor. With a significant increase in the CTL/Treg ratio, the combination of Ce6-based PDT and DMC-mediated immunomodulation adequately achieved spatiotemporal regulation and remodeling of the TME, as well as improved primary tumor and in situ lung metastasis suppression with the aid of PD-1 antibody.

Objective:To explore the relationship between irritable bowel syndrome (IBS) and premature ejaculation (PE) from 5-HT; To predict the natural drugs with therapeutic effect.Methods:Targets related to IBS and PE were screened in the GeneCards, DisGeNET, TTD, OMIM, DrugBank databases. After removing duplicates, the two disease targets were intersected and imported into STRING platform, and the protein interaction network between IBS and PE targets related to 5-HT receptor was obtained. GO enrichment analysis was carried out on the intersected targets by R language, and Coremine Medical platform was used for predicting natural drugs.Results:5-HT1A, 5-HT1B, 5-HT2A, 5-HT2C and 5-HT3A were the common targets related to 5-HT in IBS and PE. GO function enrichment yielded 250 gene function related information, mainly enriched in serotonin receptor signaling pathways, cell response to dopamine, and response to dopamine. The prediction of natural drugs obtained 14 kinds of Chinese materia medica, including Nelumbinis Semen, Nelumbinis Rhizomatis Nodus, Nelumbinis Receptaculum, Nelumbinis Stamen, Nelumbinis Folium, Nelumbinis Plumula, Ginkgo Semen, and Ginkgo Folium.Conclusions:Abnormal 5-HT levels can affect gastrointestinal motility, ejaculation latency, and glans sensitivity. Elevated central 5-HT levels are a common pathogenesis of IBS and PE. The interaction between receptors such as 5-HT1A and 5-HT3A and 5-HT can regulate gastrointestinal motility and secretion activities, intestinal nervous system, and reduce intestinal hypersensitivity; increasing the sensitivity of the 5-HT1A receptor can reduce the ejaculation threshold and promote ejaculation, while increasing the sensitivity of the 5-HT2C receptor can increase the ejaculation threshold.

Objective To investigate the value of differentiating dermatofibrosarcoma protuberans(DFSP)from neurofibroma(NF)based on MR apparent diffusion coefficient(ADC)value.Methods The enhanced MR images data of 50 patients with patho-logically or clinically confirmed DFSP(36 patients)and NF(14 patients)were analyzed retrospectively.Clinical data and characteris-tics of conventional and functional MRI,including maximum diameter,margin,depth of invasion,enhancement pattern,and ADC value,were evaluated and compared between the two groups.Chi square test,independent samples t-test or Mann-Whitney U test were used to select statistically significant parameters.New diagnostic models were established via binary logistic regression analysis.The receiver operating characteristic(ROC)curves were drawn to evaluate the diagnostic performance of these models.Results Univariate diag-nostic models were developed based on age,maximum diameter,and ADC value,while the combined model was established by logis-tic regression analysis.The area under the curve(AUC)of these models were 0.756,0.837,0.826 and 0.923,with sensitivities of 88.89%,80.56%,86.11%and 91.67%,and specificities of 64.29%,85.71%,78.57%and 92.86%,respectively.Conclusion The combined model based on ADC value,age,and maximum diameter is highly valuable for differential diagnosis between DFSP and NF.

Objective To explore the feasibility of automatic segmentation of clinical target volume(CTV)and organs at risk(OARs)for cervical cancer using AccuLearning(AL)based on geometric and dosimetric indices.Methods Seventy-five CT localization images with manual contouring data of postoperative cervical cancer were enrolled in this study.Sixty cases were randomly selected to trained to generate automatic segmentation model by AL,and the CTV and OARs of the remaining 15 cases were automatically contoured.Radiotherapy plans on the automatic segmentation contours were imported on the CT images of manual contours.The efficiency,Dice similarity coefficient(DSC),Hausdorff distance(HD)and dosimetric parameters were compared between the two methods.Results The time of automatic segmentation was significantly shorter than that of the manual contour(P<0.05).The DSC of all structures were≥0.87.The HD of bowel bag and rectum were about 10 mm,and that of the rest of OARs were less than 5 mm.CTV(D98,V90% ,V95% ,Dmean,HI),bowel bag(V50)and bladder(V50)had significant differences in dosimetric comparison(P<0.05).Conclusion The automatic segmentation model based on AL can improve the efficiency of radiotherapy.Automatic segmentation of OARs has the potential of clinical application,while that of CTV still needs to be further modified.

Objective To explore the correlation between intestinal dose and acute radiation enteritis(ARE)in patients with cervical cancer received concurrent chemoradiotherapy,and optimize the dose limit of intestinal tissue.Methods 158 cervical cancer patients received concurrent chemoradiotherapy from 2014 to 2019 were selected in this study.According to CTCAE 5.0,patients with ARE≥grade 2 were classified as ARE≥grade 2 group,otherwise classified as ARE0.7,P<0.05).Conclusions For patients with cervical cancer received concurrent chemoradiotherapy,the dose of bowelbag V5 and V40 should be considered to rationally optimize the dose of bowelbag in the radiotherapy plan,so as to reduce the incidence of ARE≥grade 2.