ObjectiveTo investigate the effect of laminin subunit α3 （LAMA3） on the epithelial-mesenchymal transition （EMT）， invasion， and metastasis abilities of pancreatic cancer （PC）. MethodsA comprehensive analysis was performed for tumor- and EMT-related databases to identify the EMT genes associated with PC， especially LAMA3. The methods of qRT-PCR and Western blot were used to measure the expression level of LAMA3 in PC tissue and cell lines； immunofluorescence assay was used to determine the localization of LAMA3 in PANC-1 cells； Transwell assay was used to investigate the effect of LAMA3 on the invasion and migration abilities of PC cells. The t-test was used for comparison of continuous data between groups. ResultsThe analysis of the TCGA database identified 3 EMT-related oncogenes for PC， i.e.， LAMA3， AREG， and SDC1. The LASSO-Cox regression model showed that LAMA3 had the most significant impact on the prognosis of PC （risk score=0.256 1×LAMA3+0.043 1×SDC1+0.071 4×AREG）. The Cox model and nomogram showed that the high expression of LAMA3 was an independent risk factor for the poor prognosis of PC （hazard ratio=1.32， 95% confidence interval： 1.07‍ ‍—‍ 1.62， P<0.01）. Experimental results showed that there was a significant increase in the expression of LAMA3 in pancreatic cancer tissue compared with the normal pancreatic tissue. Compared with the HPDE cell line， there were varying degrees of increase in the expression of LAMA3 in pancreatic cancer AsPC-1， BxPC-3， PANC-1， MIA PaCa-2， and SW1990 cell lines， with the highest expression level in PANC-1 cells. The enrichment analysis showed that LAMA3 was associated with the biological processes and signaling pathways such as EMT， collagen metabolism， extracellular matrix degradation， the TGF-β pathway， and the PI3K pathway. After the knockdown of LAMA3， there were significant reductions in the expression levels of N-Cadherin， Vimentin， and Snail， while there was a significant increase in the expression level of E-Cadherin. Transwell assay showed that there were significant reductions in the invasion and migration abilities of PANC-1 cells after the knockdown of LAMA3. ConclusionLAMA3 is highly expressed in PC and can promote the EMT， invasion， and migration of PC cells， and therefore， LAMA3 may be used as a novel diagnostic marker and a new therapeutic target for PC.

The analysis presented here is based on the blood components of Guanxin Qiwei tablets, the key anti-atherosclerosis pathway of Guanxin Qiwei tablets was screened by network pharmacology, and the anti-atherosclerosis mechanism of Guanxin Qiwei tablets was clarified and verified by cell experiments. HPLC-Q-Exactive-MS/MS technique was used to analyze the components of Guanxin Qiwei tablets into blood, to determine the precise mass charge ratio of the compounds, and to conduct a comprehensive analysis of the components by using secondary mass spectrometry fragments and literature comparison. Finally, a total of 42 components of Guanxin Qiwei tablets into blood were identified. To better understand the interactions, we employed the Swiss Target Prediction database to predict the associated targets. Atherosclerosis (AS) disease targets were searched in disease databases Genecard, OMIM and Disgent, and 181 intersection targets of disease targets and component targets were obtained by Venny 2.1.0 software. Protein interactions were analyzed by String database. The 32 core targets were selected by Cytscape software. Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed in DAVID database. It was found that the anti-atherosclerosis pathways of Guanxin Qiwei tablets mainly include lipid metabolism and atherosclerosis and AGE-RAGE signaling pathway in diabetic complications and other signal pathways. The core targets and the core compounds were interlinked, and it was found that cryptotanshinone and tanshinone ⅡA in Guanxin Qiwei tablets were well bound to TNF, PPARγ, AKT1, PTG2 and other targets. The lipid metabolism and atherosclerotic pathway was verified using human hl-7702 hepatocytes. This study preliminarily identified the potential pharmacodynamic components of Guanxin Qiwei tablets in the treatment of AS diseases and predicted their pathways of action, and verified the relationship between regulating lipid metabolism and atherosclerosis of Guanxin Qiwei tablets in vitro, providing a reference for the further study of the pharmacodynamic material basis and mechanism of action of this prescription. This experiment was approved by the Medical Ethics Committee of Inner Mongolia Medical University (No. YKD202401262).

As new evidence emerges, treatment strategies toward the functional cure of chronic hepatitis B are evolving. In 2019, a panel of national hepatologists published a Consensus Statement on the functional cure of chronic hepatitis B. Currently, an international group of hepatologists has been assembled to evaluate research since the publication of the original consensus, and to collaboratively develop the updated statements. The 2.0 Consensus was aimed to update the original consensus with the latest available studies, and provide a comprehensive overview of the current relevant scientific literatures regarding functional cure of hepatitis B, with a particular focus on issues that are not yet fully clarified. These cover the definition of functional cure of hepatitis B, its mechanisms and barriers, the effective strategies and treatment roadmap to achieve this endpoint, in particular new surrogate biomarkers used to measure efficacy or to predict response, and the appropriate approach to pursuing a functional cure in special populations, the development of emerging antivirals and immunomodulators with potential for curing hepatitis B. The statements are primarily intended to offer international guidance for clinicians in their practice to enhance the functional cure rate of chronic hepatitis B.

As new evidence emerges, treatment strategies toward the functional cure of chronic hepatitis B are evolving. In 2019, a panel of national hepatologists published a Consensus Statement on the functional cure of chronic hepatitis B. Currently, an international group of hepatologists has been assembled to evaluate research since the publication of the original consensus, and to collaboratively develop the updated statements. The 2.0 Consensus was aimed to update the original consensus with the latest available studies, and provide a comprehensive overview of the current relevant scientific literatures regarding functional cure of hepatitis B, with a particular focus on issues that are not yet fully clarified. These cover the definition of functional cure of hepatitis B, its mechanisms and barriers, the effective strategies and treatment roadmap to achieve this endpoint, in particular new surrogate biomarkers used to measure efficacy or to predict response, and the appropriate approach to pursuing a functional cure in special populations, the development of emerging antivirals and immunomodulators with potential for curing hepatitis B. The statements are primarily intended to offer international guidance for clinicians in their practice to enhance the functional cure rate of chronic hepatitis B.

As new evidence emerges, treatment strategies toward the functional cure of chronic hepatitis B are evolving. In 2019, a panel of national hepatologists published a Consensus Statement on the functional cure of chronic hepatitis B. Currently, an international group of hepatologists has been assembled to evaluate research since the publication of the original consensus, and to collaboratively develop the updated statements. The 2.0 Consensus was aimed to update the original consensus with the latest available studies, and provide a comprehensive overview of the current relevant scientific literatures regarding functional cure of hepatitis B, with a particular focus on issues that are not yet fully clarified. These cover the definition of functional cure of hepatitis B, its mechanisms and barriers, the effective strategies and treatment roadmap to achieve this endpoint, in particular new surrogate biomarkers used to measure efficacy or to predict response, and the appropriate approach to pursuing a functional cure in special populations, the development of emerging antivirals and immunomodulators with potential for curing hepatitis B. The statements are primarily intended to offer international guidance for clinicians in their practice to enhance the functional cure rate of chronic hepatitis B.

OBJECTIVE To establish a method for determining the contents of clopidogrel （CLP）， clopidogrel carboxylate （CLP-C）， clopidogrel acyl-β-D-glucuronide （CLP-G） and contents of clopidogrel active metabolite （CAM） in rat plasma， and to investigate their in vivo pharmacokinetic characteristics. METHODS The Shisedo CAPCELL ADME column was used with a mobile phase consisting of water and acetonitrile （both containing 0.1% formic acid） in a gradient elution. The flow rate was 0.4 mL/min， and the column temperature was maintained at 20 ℃. The injection volume was 2 μL. The analysis was performed in positive ion mode using electrospray ionization with multiple reaction monitoring. The ion pairs for quantitative analysis were m/z 322.1→211.9 （for CLP）， m/z 308.1→197.9 （for CLP-C）， m/z 322.1→154.8 （for CLP-G）， m/z 504.1→154.9 [for racemic CAM derivative （CAMD）]. Six rats were administered a single intragastric dose of CLP （10 mg/kg）. Blood samples were collected before medication and at 0.08， 0.33， 0.66， 1， 2， 4， 6， 10， 23 and 35 hours after medication. The established method was used to detect the serum contents of various components in rats. Pharmacokinetic parameters were then calculated using WinNonlin 6.1 software. RESULTS The linear ranges for CLP， CLP-C and CAMD were 0.08-20.00， 205.00-8 000.00， and 0.04-25.00 ng/mL， respectively （r≥0.990）. The relative standard deviations for both intra-day and inter-day precision tests were all less than 15%， and the relative errors for accuracy ranged from －11.68% to 14.40%. The coefficients of variation for the matrix factors were all less than 15%， meeting the requirements for bioanalytical method validation. The results of the pharmacokinetic study revealed that， following a single intagastric administration of CLP in rats， the exposure to the parent CLP in plasma was extremely low. Both the area under the drug concentration-time curve （AUC0-35 h） and the peak concentration of the parent CLP were lower than those of its metabolites. The AUC0-35 h of the active metabolite CAM was approximately 43 times that of CLP， though it had a shorter half-life （2.53 h）. The inactive metabolite CLP-C exhibited the highest exposure level， but it reached its peak concentration the latest and was eliminated slowly. The AUC0-35 h of CLP-G was about four times that of CAM， and its half-life was similar to that of CLP-C. CONCLUSIONS This study successfully established an liquid chromatography-tandem mass spectrometry method for the determination of CLP and its three metabolites， and revealed their pharmacokinetic characteristics in rats. Specifically， the parent drug CLP was rapidly eliminated， while the inactive metabolites CLP-C and CLP-G exhibited long half-lives， and active metabolite CAM displayed a transient exposure pattern.

Lung cancer is the most common malignant tumor worldwide, ranking first in both incidence and mortality rates. According to the latest statistics from the International Agency for Research on Cancer (IARC), approximately 2.5 million new cases and around 1.8 million deaths from lung cancer occurred in 2022, placing a tremendous burden on global healthcare systems. The high mortality rate of lung cancer is closely linked to its subtle early symptoms, which often lead to diagnosis at advanced stages. This not only complicates treatment but also results in substantial economic losses. Current treatment options for lung cancer include surgery, radiotherapy, chemotherapy, targeted drug therapy, and immunotherapy. Among these, immunotherapy has emerged as the most groundbreaking advancement in recent years, owing to its unique antitumor mechanisms and impressive clinical benefits. Unlike traditional therapies such as radiotherapy and chemotherapy, immunotherapy activates or enhances the patient’s immune system to recognize and eliminate tumor cells. It offers advantages such as more durable therapeutic effects and relatively fewer toxic side effects. The main approaches to lung cancer immunotherapy include immune checkpoint inhibitors, tumor-specific antigen-targeted therapies, adoptive cell therapies, cancer vaccines, and oncolytic virus therapies. Among these, immune checkpoint inhibitors and tumor-specific antigen-targeted therapies have received approval from the U.S. Food and Drug Administration (FDA) for clinical use in lung cancer, significantly improving outcomes for patients with advanced non-small cell lung cancer. Although other immunotherapy strategies are still in clinical trials, they show great potential in improving treatment precision and efficacy. This article systematically reviews the latest research progress in lung cancer immunotherapy, including the development of novel immune checkpoint molecules, optimization of treatment strategies, identification of predictive biomarkers, and findings from recent clinical trials. It also discusses the current challenges in the field and outlines future directions, such as the development of next-generation immunotherapeutic agents, exploration of more effective combination regimens, and the establishment of precise efficacy prediction systems. The aim is to provide a valuable reference for the continued advancement of lung cancer immunotherapy.

To compare the clinical efficacy of intralesional corticosteroid injection combined with topical corticosteroids versus topical corticosteroids alone in patients with idiopathic granulomatous mastitis (IGM).

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

ObjectiveTo review the characteristics of interbrain synchrony between individuals with autism spectrum disorder (ASD) and healthy individuals during interactions. MethodsResearches on interbrain synchrony during interactions in individuals with ASD were retrieved from databases such as PubMed, Web of Science, Scopus and CNKI in November, 2023. Researches were screened and the relevant data were extracted. The quality of the methodology was evaluated using critical appraisal tool for analytic cross sectional study. ResultsFive researches were returned, publicated mainly from 2020 to 2023, including 130 individuals with ASD. Interbrain synchrony was lower during the interaction task in the individuals with ASD compared with the healthy, mainly involving the prefrontal and temporo-parietal joint regions; as well as the interbrain synchrony of theta, alpha and beta bands of electroencephalography. There was difference in interbrain synchrony between genders in individuals with ASD; furthermore, abnormal interbrain synchrony in individuals with ASD associated with social impairment. ConclusionInterbrain synchrony deficits may be a potential neural mechanism for social impairment in individuals with ASD, and the abnormalities mainly happen in the brain areas related with mirror nervous system and theories of mind network.