Objective: To investigate the microbial mechanisms of Banxia Xiexin Decoction (半夏泻心汤, BXXXD) in the treatment of esophageal precancerous lesions. Methods: A total of 30 specific pathogen-free (SPF) grade female C57BL/6J mice were randomly assigned to a control group (n = 6) and a 4-nitroquinoline 1-oxide (4-NQO)-exposed group (n = 24). Esophageal precancerous lesions were induced by providing the 4-NQO-exposed group with 4-NQO in drinking water (100 μg/mL) for 17 consecutive weeks, whereas control group received sterile drinking water. After model establishment, the mice in 4-NQO-exposed group were further randomized into model group and three BXXXD-treated groups: low-dose (BXXXD-L, 3.7 g/kg), medium-dose (BXXXD-M, 7.4 g/kg), and high-dose (BXXXD-H, 14.8 g/kg) groups (n = 6 per group). During the subsequent intervention period, mice in control and model groups were gavaged with sterile water, while mice in BXXXD groups were gavaged once daily with the corresponding dose of BXXXD aqueous extract for 4 weeks. Histopathological changes in esophageal tissues were observed by hematoxylin and eosin (HE) staining. The fecal and esophageal microbiota were profiled via 16S rDNA high-throughput sequencing to evaluate bacterial diversity, community structure, and co-occurrence networks. BXXXD chemical fingerprints were analyzed using ultra-high-performance liquid chromatography coupled with quadrupole QExactive Orbitrap mass spectrometry (UHPLC-QE-MS). Serum short-chain fatty acids (SCFA) level was quantified by targeted metabolomics using gas chromatography-mass spectrometry (GC-MS). Transcriptomic analysis of esophageal tissues was performed to assess gene expression profiles. Results: Compared with model group, BXXXD-M group exhibited reduced mucosal hyperplasia and more orderly epithelial cell arrangement, with superior therapeutic effects in comparison with both BXXXD-L and BXXXD-H groups (P < 0.01). Microbiota analysis revealed that BXXXD increased the abundance of beneficial Enterococcus and reduced pathogenic Escherichia-Shigella in the esophagus. In the gut, BXXXD elevated the relative abundance of beneficial taxa, including Lactobacillus, Dubosiella, Bacteroides, and Faecalibacterium. Targeted metabolomics showed that BXXXD significantly reduced total serum SCFA level (P < 0.01). Transcriptomic analysis indicated that BXXXD downregulated the expression of genes associated with the progression, migration, and invasion of esophageal cancer, which were identified as kallikrein-related peptidase 6 (Klk6), defensin beta 4 (Defb4), family with sequence similarity 3 member B (Fam3b), carboxypeptidase A4 (Cpa4), serum amyloid A1 (Saa1), and chitinase-like 1 (Chil1) (P < 0.05). Conclusion BXXXD may reduce the expression levels of esophageal cancer-related genes and improve esophageal precancerous lesions through modulation of the gut microbiota and metabolites.

OBJECTIVE To introduce the development of an intelligent prescription review decision-support system for anti-tumor drugs and assess its clinical application outcomes. METHODS Relevant data sources， including national and local pharmaceutical administration policies， clinical practice guidelines/consensus， hospital information systems data， and genetic testing results， were integrated. Adhering to the principles of structure， standardization and dynamic updating， a knowledge base covering chemotherapeutic， targeted and immunotherapeutic agents was constructed using a dual-dimensional modeling approach that combined “drug attributes” and “clinical contexts”. This knowledge base was then embedded into the hospital’s electronic medical order system to establish the prescription review decision-support system. The application and performance of the system were evaluated at Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine. RESULTS A knowledge base containing 18 318 prescription review rules for anti-tumor drugs was constructed， and a closed-loop prescription review system was successfully established， encompassing pre-prescription real-time intervention， in-process interactive review， and post-prescription evaluation and analysis. From 2021 to 2024， the system generated a total of 57 879 alerts for prescriptions of five typical categories of anti-tumor drugs. For platinum-containing prescriptions， 22 577 alerts were generated， with Cisplatin for injection （lyophilized） being the most frequently alerted drug （13 445 alerts）， and “ototoxicity risk due to combined use” alerts remained high （7 682 alerts）. For methotrexate-containing prescriptions， 3 721 alerts were recorded， primarily related to “precaution-related issues” （76.4%， 2 843/3 721）. For doxorubicin-containing prescriptions， 17 301 alerts were triggered， primarily related to “dosage and administration” （14 315 alerts）. For human epidermal growth factor receptor 2-targeted agents-containing prescriptions， 1 007 alerts were issued， mostly related to “reimbursement restrictions” （956 alerts）. For programmed death-1/programmed death-ligand 1 inhibitors-containing prescriptions， the alerts increased year by year， totaling 13 273 alerts， primarily related to “inappropriate indication” （9 118 alerts）. Over the 4 years， the physician response rates to system alerts were 21.4%， 27.1%， 33.5% and 51.6%， respectively. CONCLUSIONS An intelligent decision-support system for anti-tumor drug prescription review， encompassing a closed-loop process of “real-time pre-event intervention， interactive in-event prescription review， post-event evaluation and analysis”， has been successfully constructed and implemented throughout the entire workflow. There is a discernible trend in this hospital， where the focus on monitoring anti-tumor drugs is shifting towards immunotherapy drugs. Additionally， the acceptance rate of physicians regarding prescription review opinions has been steadily increasing year by year.

ObjectiveThis paper aims to observe the syndrome improvement and negative antigen conversion rate of Qingxuan Daozhi formula in the treatment of influenza in children （heat accumulation in the lung and stomach syndrome）. MethodsThrough a multi-center randomized controlled methodology design，confirmed influenza cases were collected from October 2022 to April 2023 in the pediatrics department of eight hospitals，such as Dongfang Hospital of Beijing University of Chinese Medicine. A total of 180 children with influenza and heat accumulation in the lung and stomach syndrome conforming to the standard were recruited through the clinic. The sick children meeting the inclusion criteria were randomly divided into groups by a block-randomized method. The children in the experimental group were treated with Qingxuan Daozhi formula for five days，and those in the control group were treated with Oseltamivir Phosphate Granules for five days. The primary efficacy indicator was the negative conversion rate of influenza antigen detection. Secondary efficacy indicators were the Canadian acute respiratory illness and flu scale （CARIFS） and the incidence of complications，severe cases， and critical cases. Follow-up observation was conducted on the day of enrollment，48 hours after medication，72 hours after medication， and （6+1） d after medication. ResultsOne hundred and eighty participants were randomly assigned to the experimental group （90 cases） or the control group （90 cases）. All participants were followed up during the study. Comparison of influenza antigen detection results in the primary efficacy indicators showed that the average time of negative influenza antigen conversion in the experimental group was （5.29±1.25） d，and that in the control group was （5.40±1.68） d，without a statistically significant difference. After five days of intervention，52 cases in the experimental group and 51 cases in the control group converted to negative，without a statistically significant difference. CARIFS score results in the secondary efficacy indicators showed that during 72 hours after intervention，there were statistically significant differences between the experimental group and the control group in three dimensions， including headache，muscle soreness， and the need for extra care （P<0.05）. On the （6+1） days after the intervention，the differences in both the experimental group and the control group were statistically significant in 10 dimensions， including sore throat，bad sleep，uncomfortable feeling，poor spirit and fatigue，crying more than usual，the need for extra care，symptom，function，influence on parents，and total score （P<0.05）. The comparison results within the group in the dimensional scores of symptom， function， and influence on parents，as well as the CARIFS total score showed that with the delay of follow-up time，scores of both groups decreased significantly，with a statistically significant difference （P<0.01）. Inter-group comparison results showed that the mean score of the experimental group was higher than that of the control group at the time of enrollment. With the progress of intervention，the score of the experimental group was significantly decreased compared with that of the control group. At the end of follow-up，the mean score of the experimental group was lower than that of the control group，with no statistically significant difference. In terms of the incidence of complications，severe cases， and critical cases， there were no complications，severe cases， and critical cases in the two groups，without a statistically significant difference. ConclusionThe symptom improvement effect and negative antigen conversion rate of Qingxuan Daozhi formula in the treatment of influenza in children （heat accumulation in the lung and stomach syndrome） are not inferior to Oseltamivir Phosphate granules， and children's acceptance is better. It can be more widely used in clinical treatment of influenza in children （heat accumulation in the lung and stomach syndrome）.

Background Microparticles (MPs) are one of the main medium of inflammatory reaction with an important role in atherosclerotic progression. Studies on association of air pollution exposure and levels of peripheral blood MPs are limited among human. Objective To evaluate the effects of short-term exposure to air pollution on levels of peripheral blood MPs. Method A panel of 73 healthy adults was followed with 4 repeated follow-ups in Beijing, China, from November 2014 to January 2016. During each visit, we collected questionnaire information, fasting venous blood, urine, and exposures to fine particulate matter (PM_2.5), black carbon, nitric oxide, nitrogen dioxide, nitrogen oxide, sulfur dioxide, carbon monoxide, and ozone. We used linear mixed-effect models to analyze associations of air pollution exposure with levels of total MPs (TMPs) and MPs derived from various cells. Stratified analysis was conducted by levels of C-reactive protein (CRP) and malondialdehyde (MDA). Results The results showed significant associations between air pollution exposure and peripheral blood TMPs at 2 h-6 d prior to the follow-ups (P<0.05), while no statistical associations were found for MPs derived from different cell types. Significant increases in TMPs of 7.8% (95%CI: 0.7%, 15.3%) and 14.3% (95%CI: 2.8%, 27.2%) were observed with each interquartile range (IQR) increase in PM_2.5 (IQR=64.9 μg·m⁻³) at prior 18 h and NO (IQR=40.5 μg·m⁻³) at prior 48 h. Among participants with low levels of CRP and MDA, significantly positive associations were observed between air pollution exposure and levels of TMPs (P<0.05). Conclusion Short-term exposure to air pollution is significantly associated with increased levels of circulating MPs in healthy adults, and in people with lower systemic inflammation, peripheral blood MPs levels are more easily affected after exposure to air pollutants.

A natural experiment is a causal inference study design grounded in real-world research. Its core concept is to use quasi-random variation in exposure generated by external factors to evaluate the effects of interventions or exposures on outcomes. It is particularly suitable for research settings in which randomized controlled trials （RCTs） are infeasible or ethically constrained， and it combines causal inference capacity with relatively strong external validity. This article provides an overview of the definition， key features， and current application status of natural experiments， and proposes the application scenarios for applying natural experiment strategies to the evaluation of therapeutic effects in traditional Chinese medicine （TCM）， including policy implementation or policy change evaluation， assessment of variations in clinical practice within hospitals， and evaluation of differences in resource allocation across regions or institutions. The design pathway includes starting from clinical or policy-related TCM questions， systematically collecting relevant data， performing statistical modeling and effect estimation， and interpreting effect estimates in the context of clinical practice. It further analyzes the advantages and challenges of using natural experiments in TCM.

As one of the common chronic bacterial infections, Helicobacter pylori (Hp) infection is a key pathogenic factor of chronic gastritis, peptic ulcer and gastric cancer. In the formation of gastric ulcer, Hp virulence factors directly damage the gastric mucosal barrier, induce the local inflammation and immune response, interfere with the regulation of gastric acid secretion, and ultimately destroy the mucosal stability. In the occurrence of gastric cancer, Hp-driven chronic inflammation is the basis of inflammation-cancer transformation, and it induces the genomic instability and epigenetic changes by interfering with key signaling pathways in host cells, thereby promoting malignant transformation. This paper systematically reviews the related mechanisms of Hp-induced gastric ulcer and gastric cancer in recent years, holding great significance for the development of new intervention strategies and the precise prevention and treatment of gastric cancer.

A natural experiment is a causal inference study design grounded in real-world research. Its core concept is to use quasi-random variation in exposure generated by external factors to evaluate the effects of interventions or exposures on outcomes. It is particularly suitable for research settings in which randomized controlled trials （RCTs） are infeasible or ethically constrained， and it combines causal inference capacity with relatively strong external validity. This article provides an overview of the definition， key features， and current application status of natural experiments， and proposes the application scenarios for applying natural experiment strategies to the evaluation of therapeutic effects in traditional Chinese medicine （TCM）， including policy implementation or policy change evaluation， assessment of variations in clinical practice within hospitals， and evaluation of differences in resource allocation across regions or institutions. The design pathway includes starting from clinical or policy-related TCM questions， systematically collecting relevant data， performing statistical modeling and effect estimation， and interpreting effect estimates in the context of clinical practice. It further analyzes the advantages and challenges of using natural experiments in TCM.

Objective:To investigate the effect of ultrasound-guided scalp nerve block (SNB) combined with dexmedetomidine on cerebral blood flow after craniotomy in patients with acute traumatic brain injury (TBI).Methods:A randomized controlled design was conducted. Patients aged 25-65 years, with ASA physical status I–III and Glasgow Coma Scale scores of 9-12, who underwent craniotomy for acute TBI at Kunshan Traditional Chinese Medicine Hospital between January 2024 and February 2025 were selected. Patients with unstable vital signs, cranial tumors, cardiovascular diseases, local anesthetic allergies, or infections at the puncture site were excluded. Using a random number table, patients were divided into two groups: the ultrasound-guided SNB combined with dexmedetomidine group (SD group) and the dexmedetomidine-alone group (D group). General clinical data, peak systolic velocity (PSV), mean blood flow velocity (MBFV), intracranial pressure (ICP), S100 calcium-binding protein beta (S-100β protein), neuron-specific enolase (NSE) levels, and postoperative complications were compared. Dynamic changes in PSV and MBFV were analyzed using repeated measures analysis of variance, while inter-group comparisons used independent sample t-tests. Results:A total of 79 patients were included, with 40 in the SD group and 39 in the D group. There were no significant differences in general clinical data between the two groups (all P>0.05). In the D group, PSV and MBFV at T 1 and T 2 were significantly higher than at T0 [(125.04±20.43) cm/s vs. (126.83±21.76) cm/s vs. (110.63±18.49) cm/s, P=0.001; (61.75±8.34) cm/s vs. (62.81±8.54) cm/s vs. (57.82±6.93) cm/s, P=0.017], whereas no significant differences were observed in the SD group (all P>0.05). PSV, MBFV, ICP, S-100β protein, and NSE levels at T1 and T2 in the SD group were lower than those in the D group (all P<0.05). The incidence of postoperative hypertension, agitation, and the use rate of vasoactive drugs were also lower in the SD group compared to the D group (all P<0.05). Conclusion:The application of ultrasound-guided SNB combined with dexmedetomidine in TBI patients after craniotomy can help stabilize cerebral blood flow and ICP, mitigate neuronal injury, and reduce the incidence of postoperative complications.

Objective To explore common target genes related to aging and osteoporosis using data from public databases and to screen for small molecule compounds with potential therapeutic effects.Methods Osteoporosis datasets GSE56814 and GSE56815 were downloaded and merged from the public gene expression database(Gene Expression Omnibus(GEO)).Senescent genes were selected and merged from the genecard database and the cell age database.Data cleaning and differential gene selection were performed using R software,and a volcano plot was created.Weighted gene co-expression network analysis was performed to screen out key modules and genes,and the machine learning methods were employed to screen target genes.A Venn diagram was drawn using the the Microbioinformatics platform,and cytoscape software was used to visualise protein interactions results.Interaction analysis of differentially encoded proteins was carried out using the STRING database,and prediction of small molecule compounds was carried out using Cmap database.Finally,Receiver operating characteristic(ROC)curves were plotted to find out the most meaningful target genes,followed by the establishment of a logistic regression model and the creation of a nomogram.Results A total of 127 differential genes were screened using the limma package.Weighted gene co-expression network analysis was performed on the differential genes and 103 highly expressed genes were screened.Three machine learning methods,lasso regression,support vector machine and random forest model,were used to finally obtain four target genes:FOXO3,HIRA,CBX5 and RAD1.The nomogram and calibration curves showed good predictive results.Five small molecule compounds with potential therapeutic effects were identified using the Cmap database:sakuraflavin(O-methylated isoflavone),XMD-885,kangaroo hyoscyamine,everolimus and XMD-1150.Conclusion FOXO3 and HIRA genes have now been confirmed to be the common target genes for aging and osteoporosis,and sakuraflavin has potential therapeutic effects on both conditions.

Adolescents and young adults (AYAs) are one of the major populations susceptible to tuberculosis. However, little is known about the unique characteristics and diagnostic biomarkers of tuberculosis in this population. In this study, 81 AYAs were recruited, and the high-quality serum proteome of the AYAs with tuberculosis was profiled by quantitative proteomics. The data of serum proteomics indicated that the relative abundance of hemoglobin and apolipoprotein was significantly reduced in the patients with active tuberculosis (ATB). The pathway enrichment analysis showed that the downregulated proteins in the ATB group were mainly involved in the antioxidant and cell detoxification pathways, indicating extensive oxidative stress damage. Random forest (RF) and extreme gradient boosting (XGBoost) were employed to evaluate protein importance, which yielded a set of candidate proteins that can distinguish between ATB and non-ATB. The analysis with the support vector machine algorithm (recursive feature elimination) suggested that the combination of apolipoprotein A-I (APOA1), hemoglobin subunit beta (HBB), and hemoglobin subunit alpha-1 (HBA1) had the highest accuracy and sensitivity in diagnosing ATB. Meanwhile, the levels of hemoglobin (HGB) and albumin (ALB) can be used as blood biochemical indicators to evaluate changes in the protein levels of APOA1 and HBB. This study established the serum proteome landscape of AYAs with tuberculosis and identified new biomarkers for the diagnosis of tuberculosis in this population.
Humans ; Proteomics/methods* ; Biomarkers/blood* ; Adolescent ; Young Adult ; Apolipoprotein A-I/blood* ; Machine Learning ; Tuberculosis/blood* ; Proteome/analysis* ; Male ; Hemoglobins/analysis* ; Female ; Blood Proteins/analysis* ; Adult