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.

ObjectiveTo explore the molecular mechanism of aerobic exercise to improve hippocampal neuronal degeneration by regulating tryptophan metabolic pathway. Methods60 SPF-grade C57BL/6J male mice were divided into a young group (2 months old, n=30) and a senile group (12 months old, n=30), and each group was further divided into a control group (C/A group, n=15) and an exercise group (CE/AE group, n=15). An aerobic exercise program was used for 8 weeks. Learning memory ability was assessed by Y-maze, and anxiety-depression-like behavior was detected by absent field experiment. Hippocampal Trp levels were measured by GC-MS. Nissl staining was used to observe the number and morphology of hippocampal neurons, and electron microscopy was used to detect synaptic ultrastructure. ELISA was used to detect the levels of hippocampal Trp,5-HT, Kyn, KATs, KYNA, KMO, and QUIN; Western blot was used to analyze the activities of TPH2, IDO1, and TDO enzymes. ResultsGroup A mice showed significant decrease in learning and memory ability (P<0.05) and increase in anxiety and depressive behaviors (P<0.05); all of AE group showed significant improvement (P<0.05). Hippocampal Trp levels decreased in group A (P<0.05) and increased in AE group (P<0.05). Nidus vesicles were reduced and synaptic structures were degraded in group A (P<0.05), and both were significantly improved in group AE (P<0.05). The levels of Trp, 5-HT, KATs, and KYNA were decreased (P<0.05) and the levels of Kyn, KMO, and QUIN were increased (P<0.05) in group A. The activity of TPH2 was decreased (P<0.05), and the activities of IDO1 and TDO were increased (P<0.05). The AE group showed the opposite trend. ConclusionThe aging process significantly reduces the learning memory ability and increases the anxiety-depression-like behavior of mice, and leads to the reduction of the number of nidus vesicles and degenerative changes of synaptic structure in the hippocampus, whereas aerobic exercise not only effectively enhances the spatial learning memory ability and alleviates the anxiety-depression-like behavior of aging mice, but also improves the morphology and structure of neurons in hippocampal area, which may be achieved by the mechanism of regulating the tryptophan metabolic pathway.

This study aims to explore the pharmacodynamic material basis of Jinbei Oral Liquid(JBOL) against idiopathic pulmonary fibrosis(IPF) based on serum pharmacochemistry and network pharmacology. The ultra-high performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry(UHPLC-Q-TOF-MS/MS) technology was employed to analyze and identify the components absorbed into rat blood after oral administration of JBOL. Combined with network pharmacology, the study explored the pharmacodynamic material basis and potential mechanism of JBOL against IPF through protein-protein interaction(PPI) network construction, "component-target-pathway" analysis, Gene Ontology(GO) functional enrichment, and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis. First, a total of 114 compounds were rapidly identified in JBOL extract according to the exact relative molecular mass, fragment ions, and other information of the compounds with the use of reference substances and a self-built compound database. Second, on this basis, 70 prototype components in blood were recognized by comparing blank serum with drug-containing serum samples, including 28 flavonoids, 25 organic acids, 4 saponins, 4 alkaloids, and 9 others. Finally, using these components absorbed into blood as candidates, the study obtained 212 potential targets of JBOL against IPF. The anti-IPF mechanism might involve the action of active ingredients such as glycyrrhetinic acid, cryptotanshinone, salvianolic acid B, and forsythoside A on core targets like AKT1, TNF, and ALB and thereby the regulation of multiple signaling pathways including PI3K/AKT, HIF-1, and TNF. In conclusion, JBOL exerts the anti-IPF effect through multiple components, targets, and pathways. The results would provide a reference for further study on pharmacodynamic material basis and pharmacological mechanism of JBOL.
Drugs, Chinese Herbal/pharmacokinetics* ; Animals ; Tandem Mass Spectrometry ; Network Pharmacology ; Rats ; Chromatography, High Pressure Liquid ; Rats, Sprague-Dawley ; Male ; Idiopathic Pulmonary Fibrosis/metabolism* ; Humans ; Administration, Oral ; Protein Interaction Maps/drug effects* ; Signal Transduction/drug effects*

OBJECTIVES: To evaluate the application value of genetic newborn screening (gNBS) in the Yunnan region. METHODS: A prospective study was conducted with a random selection of 3 001 newborns born in the Yunnan region from February to December 2021. Traditional newborn screening (tNBS) was used to test biochemical indicators, and targeted next-generation sequencing was employed to screen 159 genes related to 156 diseases. Positive-screened newborns underwent validation and confirmation tests, and confirmed cases received standardized treatment and long-term follow-up. RESULTS: Among the 3 001 newborns, 166 (5.53%) were initially positive for genetic screening, and 1 435 (47.82%) were genetic carriers. The top ten genes with the highest variation frequency were GJB2 (21.29%), DUOX2 (7.27%), HBA (6.14%), GALC (3.63%), SLC12A3 (3.33%), HBB (3.03%), G6PD (2.94%), SLC25A13 (2.90%), PAH (2.73%), and UNC13D (2.68%). Among the initially positive newborns from tNBS and gNBS, 33 (1.10%) and 47 (1.57%) cases were confirmed, respectively. A total of 48 (1.60%) cases were confirmed using gNBS+tNBS. The receiver operating characteristic curve analysis demonstrated that the areas under the curve for tNBS, gNBS, and gNBS+tNBS in diagnosing diseases were 0.866, 0.982, and 0.968, respectively (P<0.05). DeLong's test showed that the area under the curve for gNBS and gNBS+tNBS was higher than that for tNBS (P<0.05). CONCLUSIONS gNBS can expand the range of disease detection, and its combined use with tNBS can significantly shorten diagnosis time, enabling early intervention and treatment.
Humans ; Infant, Newborn ; Neonatal Screening ; Genetic Testing ; Female ; Male ; Follow-Up Studies ; Prospective Studies ; China

Objective To evaluate the application value of four-dimensional CT(4D-CT)in the preoperative localization of primary hyperparathyroidism(PHPT). Methods A retrospective analysis was conducted on the clinical data and parathyroid 4D-CT images of 63 patients who underwent PHPT surgery at Peking Union Medical College Hospital between April 2020 and April 2023.Based on the clinical experience of the hospital's surgeons,parathyroid lesions were categorized into six anatomical regions:around the upper pole of the thyroid,posterior to the mid-thyroid,posterior to the lower pole of the thyroid and the tracheoesophageal groove,below the lower pole of the thyroid and the suprasternal fossa,retrosternal anterior mediastinum,and other rare locations.All images were independently analyzed by two experienced radiologists,with discrepancies resolved through discussion led by a senior radiologist.Using pathological results as the gold standard,the accuracy,sensitivity,specificity,positive predictive value(PPV),negative predictive value(NPV),Youden index,positive likelihood ratio(PLR),and negative likelihood ratio(NLR)of preoperative 4D-CT in diagnosing PHPT were calculated. Results There were no statistically significant differences between preoperative 4D-CT and surgical localization in the following regions:around the upper pole of the thyroid(χ²=0.500,P=0.480),posterior to the mid-thyroid(χ²<0.001,P>0.999),posterior to the lower pole of the thyroid and the tracheoesophageal groove(χ²=0.571,P=0.450),below the lower pole of the thyroid and the suprasternal fossa(χ²<0.001,P>0.999),retrosternal anterior mediastinum(χ²<0.001,P>0.999),and other rare locations(χ²<0.001,P>0.999).The preoperative 4D-CT diagnosis of PHPT lesions demonstrated a sensitivity of 82.09%,specificity of 97.43%,PPV of 87.30%,NPV of 96.19%,accuracy of 94.71%,Youden index of 79.52%,PLR of 31.94,and NLR of 0.18. Conclusion Parathyroid 4D-CT demonstrates good diagnostic efficacy in the preoperative localization of PHPT.
Humans ; Hyperparathyroidism, Primary/surgery* ; Retrospective Studies ; Four-Dimensional Computed Tomography ; Male ; Female ; Middle Aged ; Adult ; Aged ; Parathyroid Glands/diagnostic imaging* ; Preoperative Period

Bovine rotavirus(BRV)is an important pathogen causing diarrhea in calves.To understand the genomic charac-teristics and genetic variations in bovine rotavirus,and to further enrich data on the biological characteristics of rotavirus,we aimed to amplify 11 gene segments of the isolated and cultured G6P[1]bovine rotavirus BLL strain,perform whole genome se-quencing,and analyze the molecular characteristics.MEGA7.0 and DNAMAN software were used for homology and typing a-nalysis,and the whole genome phylogenetic tree was constructed to analyze genetic evolution relationships.The complete geno-type of the BLL strain was G6-P[1]-I2-R2-C2-M2-A3-N2-T6-E2-H3.Phylogenetic analysis of the VP7 and VP4 genes of the BLL strain showed that the VP7 gene had the highest homology with RVA/Cow-wt/HB01/China/2021,and the VP4 gene of the BLL strain was in the same branch as RVA/Human-tc/ISR/Ro8059/1995.From the sequence alignment of VP8*amino acids,the sialic acid domain of the BLL strain was found to be similar to that in other P[1]strains,but different from those in other types of strains,except for residue 189,which was the same as that in Ro8059 but different from that in other strains.The results suggested that the BLL strain might potentially infect humans.Therefore,continued monitoring and study of the biological characteristics of this strain are necessary to provide more information and evidence supporting further research on the cross-species transmission of group A rotavirus in China.

The morphological characteristics of hepatocellular carcinoma(HCC)tumor margins are pivotal in influencing patient's prognosis and the selection of therapeutic strategies.This paper re-viewed the classification methods of HCC tumor margins,ranging from traditional macroscopic classifi-cations to refined classification systems based on multi-omics analysis,and analyzed the role of these classification methods in guiding the formulation of personalized treatment plans.Additionally,this paper emphasized the crucial role of three-dimensional imaging techniques in assessing tumor margin morphology and outlined future research directions,including validating the effectiveness of multi-omics classification systems and developing new imaging and molecular biomarkers to achieve more precise treatment plans and prolong patient survival.

Aim To explore the potential mechanisms underlying therapeutic effects of cordycepin in asthma by utilizing network pharmacology,molecular docking,and in vitro cellular validation.Methods The thera-peutic targets associated with asthma and the drug tar-gets of cordycepin were systematically identified through comprehensive database searches.An overlap analysis of the two gene sets was performed,followed by the construction of a protein-protein interaction(PPI)network and topological analysis to identify the core targets.The core targets were subjected to Kyoto Ency-clopedia of Genes and Genomes(KEGG)pathway a-nalysis and Gene Ontology(GO)enrichment analysis,and a drug-target-pathway network was constructed.To validate the interaction between cordycepin and core targets,molecular docking and molecular dynamics sim-ulations were conducted.Subsequently,the pharmaco-logical effects and underlying mechanisms of cordyce-pin were validated in vitro using Beas-2B cells,emplo-ying Cell Counting Kit-8(CCK-8)assay and quantita-tive real-time reverse transcription PCR(RT-qPCR).Results A total of 438 potential targets of cordycepin were identified,113 of which overlapped with asthma-related therapeutic targets.Topological analysis based on the PPI network revealed 22 core targets.Using KEGG enrichment analysis,165 significantly enriched pathways were identified,including the TNF and HIF-1 signaling pathways.Molecular docking analysis re-vealed high binding affinities between cordycepin and select core targets,which further corroborated by mo-lecular dynamics simulations.In vitro experiments showed that after cordycepin pretreatment,the upregu-lation of MAPK1,HIF1A,MTOR,MYC,IL10,and JUN mRNA was significantly rescued in HDM-stimulated Beas-2B cells.Conclusions Cordycepin exerts anti-asthmatic effects by targeting MAPK1 and other key molecules,thereby providing a scientific foundation for its further development and clinical application.

Objective:To report the nationwide surveillance results of pathogenic profiles and antimicrobial resistance patterns of Gram-positive bloodstream infections in China in 2023.Methods:The clinical isolates of Gram-posttive bacteria from blood cultures were collected in member hospitals of National Bloodstream Infection Bacterial Resistant Investigation Collaborative System（BRICS）during January to December 2023. Antimicrobial susceptibility testing was performed using the dilution method recommended by the Clinical and Laboratory Standards Institute（CLSI）. Statistical analyses were conducted using WHONET 5.6 and SPSS 25.0 software.Results:A total of 4 385 Gram-positive bacterial isolates were obtained from 60 participating center. The top five pathogens were Staphylococcus aureus（ n=1 544，35.2%），coagulase-negative Staphylococci（ n=1 441，32.9%）， Enterococcus faecium（ n=574，13.1%）， Enterococcus faecalis（ n=385，8.8%），and α-hemolytic Streptococci（ n=187，4.3%）. The prevalence of methicillin-resistant Staphylococcus aureus（MRSA）and methicillin-resistant coagulase-negative Staphylococci（MRCNS）was 26.2%（405/1 544）and 69.8%（1 006/1 441），respectively. Notably，all Staphylococci remained susceptible to glycopeptide or daptomycin. Staphylococcus aureus demonstrated excellent susceptibility（>97.0%）to cephalobiol，rifampicin，trimethoprim-sulfamethoxazole，linezolid，minocycline，tigecycline，and eravacycline. No Enterococcus exhibiting resistance to linezolid were detected. Glycopeptide resistance was uncommon but more frequent in Enterococcus faecium（resistance to vancomycin and teicoplanin：both 1.7%）compared to Enterococcus faecalis（both 0.3%）. The detection rates of MRSA and MRCNS exhibited significant regional variations across the country（ χ2=17.674 and 148.650，respectively，both P<0.001）. No vancomycin-resistant Enterococci were detected in central China. Institutional comparison demonstrated higher prevalence of MRSA（ χ2=14.111， P<0.001）and MRCNS（ χ2=4.828， P=0.028）in provincial hospitals than that in municipal hospitals. Socioeconomic analysis identified elevated detection rates of both MRSA（ χ2=18.986， P<0.001）and MRCNS（ χ2=4.477， P=0.034）in less developed regions（per capita GDP

Objective:To report the results of bacterial resistant investigation collaborative system（BRICS）on the distribution and antimicrobial resistance profile of clinical Gram-negative bacteria isolates from bloodstream infections in China in 2023，and provide reference for clinical tretment of bloodstream infections and prevention and control of bacterial resistance.Methods:The clinical isolates of Gram-negative bacteria from blood cultures in member hospitals of BRICS were collected during January 2023 to December 2023. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute（CLSI）. WHONET 5.6 and SPSS 25.0 were used to analyze the data.Results:During the study period，11 492 strains of Gram-negative bacteria were collected from 60 hospitals，of which 10 098（87.9%）were Enterobacterales and 1 394（12.1%）were non-fermentative bacteria. The top 5 bacterial species were Escherichia coli（50.0%）， Klebsiella pneumoniae（26.1%）， Pseudomonas aeruginosa（5.1%）， Acinetobacter baumannii complex（5.0%）and Enterobacter cloacae complex（4.1%）. The ESBL-producing rates in Escherichia coli， Klebsiella pneumoniae and Proteus mirablilis were 46.8%（2 685/5 741），18.3%（549/2 999）and 44.0%（77/175），respectively. The prevalence of carbapenem-resistant Escherichia coli（CREC）and carbapenem-resistant Klebsiella pneumoniae（CRKP）were 1.3%（76/5 741）and 15.0%（450/2 999）；32.9%（25/76）and 78.0%（351/450）of CREC and CRKP were sensitive to ceftazidime/avibactam combination，respectively. 94.7%（72/76）and 90.2%（406/450）of CREC and CRKP were sensitive to aztreonam/avibactam combination. Furthermore，57.9%（44/76）and 79.1%（356/450）were sensitive to imipenem/relebactam combination. The prevalence of carbapenem-resistant Acinetobacter baumannii（CRAB）complex was 64.6%（370/573），while more than 80.0% of CRAB complex was sensitive to tigecycline，eravacycline and polymyxin B. The prevalence of carbapenem-resistant Pseudomonas aeruginosa（CRPA）was 17.0%（99/581）. There were differences in the composition ratio of Gram-negative bacteria in bloodstream infections and the prevalence of important Gram-negative bacteria resistance among different regions in China，with statistically significant differences in the prevalence of CREC，CRKP，CRPA and CRAB complex（ χ2=10.6，28.6，10.8 and 19.3， P<0.05）. The prevalence of ESBL-producing Escherichia coli， CREC，CRAB complex and CRKP were higher in provincial hospitals than those in municipal hospitals（ χ2=12.5，9.8，12.7 and 57.8，all P<0.01）. Conclusions:Gram-negative bacteria are the main pathogens causing bloodstream infections in China，and Escherichia coli is ranked in the top，while the trend of Klebsiella pneumoniae increases continuously with time. CRKP infection shows a slow upward trend，CREC infecton maintains a low prevalence level，and CRAB complex infection continues to exhibit a high prevalence rate. The composition and resistance patterns of pathogens causing bloodstream infections vary to some extent across different regions and levels of hospitals in China.