ObjectiveTo investigate the mechanisms by which Mahuang Lianqiao Chixiaodoutang （MLC） improves obesity-type polycystic ovary syndrome （PCOS） through the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway. MethodsThirty-six female Sprague-Dawley （SD） rats were randomly divided into a blank control group （Con） and an obesity-type PCOS model preparation group. The model was induced by gavage with letrozole （1 mg·kg^-1） combined with a high-fat diet （HFD）. After model establishment， the obesity-type PCOS model preparation group was further divided into the model group （Mod， normal saline）， metformin group （Met， 0.3 g·kg^-1）， low-dose MLC group （MLC-L， 4.3 g·kg^-1）， medium-dose MLC group （MLC-M， 8.6 g·kg^-1）， and high-dose MLC group （MLC-H， 17.2 g·kg^-1）. Active components of MLC and targets of obesity-type PCOS were screened from databases， a protein-protein interaction （PPI） network was constructed， and gene ontology（GO）and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis was performed. The gut microbiota structure was analyzed based on 16S rRNA sequencing and correlated with network pharmacology pathways. Body weight and estrous cycle were dynamically monitored. Ovarian morphology was observed by hematoxylin-eosin （HE） staining. Cell apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling （TUNEL）. Enzyme-linked immunosorbent assay （ELISA） was used to detect levels of follicle-stimulating hormone （FSH）， luteinizing hormone （LH）， anti-Müllerian hormone （AMH）， testosterone （T）， and estradiol （E₂）. Western blot was used to detect the protein expression levels of phosphorylated PI3K/PI3K （p-PI3K/PI3K）， phosphorylated Akt/Akt （p-Akt/Akt）， B-cell lymphoma-2 （Bcl-2）， and Bcl-2-associated X protein （Bax）. ResultsNetwork pharmacology screening identified 124 active components of MLC and 408 overlapping targets between the herbal formula and the disease. Core targets such as Akt1 and Bcl-2 were revealed. As indicated by 16S rRNA sequencing， the abundances of Lachnospiraceae， Lachnoclostridium， and Dorea were increased in the MLC groups （P<0.05）， while the abundance of Veillonella was decreased （P<0.05）. KEGG correlation analysis integrating network pharmacology and gut microbiota data showed significant enrichment of the PI3K/Akt signaling pathway. Animal experiments showed that， compared with the Mod group， body weight decreased to normal levels in the Met， MLC-M， and MLC-H groups. The estrous cycle became regular. The number of corpora lutea increased and cystic follicles decreased. Serum levels of T， FSH， and LH/FSH were reduced （P<0.05， P<0.01）， while the E₂ level was increased （P<0.01）. Ovarian cell apoptosis was reduced （P<0.01）， and the protein expression levels of p-PI3K/PI3K， p-Akt/Akt， and Bcl-2 in ovarian tissue were significantly increased， whereas Bax protein expression was significantly decreased （P<0.05， P<0.01）. ConclusionMLC can regulate gut microbiota structure， effectively improve ovarian pathology in rats with obesity-type PCOS， and inhibit ovarian granulosa cell apoptosis. The mechanism may be associated with upregulation of the PI3K/Akt signaling pathway.

ObjectiveTo investigate the mechanisms by which Mahuang Lianqiao Chixiaodoutang （MLC） improves obesity-type polycystic ovary syndrome （PCOS） through the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway. MethodsThirty-six female Sprague-Dawley （SD） rats were randomly divided into a blank control group （Con） and an obesity-type PCOS model preparation group. The model was induced by gavage with letrozole （1 mg·kg^-1） combined with a high-fat diet （HFD）. After model establishment， the obesity-type PCOS model preparation group was further divided into the model group （Mod， normal saline）， metformin group （Met， 0.3 g·kg^-1）， low-dose MLC group （MLC-L， 4.3 g·kg^-1）， medium-dose MLC group （MLC-M， 8.6 g·kg^-1）， and high-dose MLC group （MLC-H， 17.2 g·kg^-1）. Active components of MLC and targets of obesity-type PCOS were screened from databases， a protein-protein interaction （PPI） network was constructed， and gene ontology（GO）and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis was performed. The gut microbiota structure was analyzed based on 16S rRNA sequencing and correlated with network pharmacology pathways. Body weight and estrous cycle were dynamically monitored. Ovarian morphology was observed by hematoxylin-eosin （HE） staining. Cell apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling （TUNEL）. Enzyme-linked immunosorbent assay （ELISA） was used to detect levels of follicle-stimulating hormone （FSH）， luteinizing hormone （LH）， anti-Müllerian hormone （AMH）， testosterone （T）， and estradiol （E₂）. Western blot was used to detect the protein expression levels of phosphorylated PI3K/PI3K （p-PI3K/PI3K）， phosphorylated Akt/Akt （p-Akt/Akt）， B-cell lymphoma-2 （Bcl-2）， and Bcl-2-associated X protein （Bax）. ResultsNetwork pharmacology screening identified 124 active components of MLC and 408 overlapping targets between the herbal formula and the disease. Core targets such as Akt1 and Bcl-2 were revealed. As indicated by 16S rRNA sequencing， the abundances of Lachnospiraceae， Lachnoclostridium， and Dorea were increased in the MLC groups （P<0.05）， while the abundance of Veillonella was decreased （P<0.05）. KEGG correlation analysis integrating network pharmacology and gut microbiota data showed significant enrichment of the PI3K/Akt signaling pathway. Animal experiments showed that， compared with the Mod group， body weight decreased to normal levels in the Met， MLC-M， and MLC-H groups. The estrous cycle became regular. The number of corpora lutea increased and cystic follicles decreased. Serum levels of T， FSH， and LH/FSH were reduced （P<0.05， P<0.01）， while the E₂ level was increased （P<0.01）. Ovarian cell apoptosis was reduced （P<0.01）， and the protein expression levels of p-PI3K/PI3K， p-Akt/Akt， and Bcl-2 in ovarian tissue were significantly increased， whereas Bax protein expression was significantly decreased （P<0.05， P<0.01）. ConclusionMLC can regulate gut microbiota structure， effectively improve ovarian pathology in rats with obesity-type PCOS， and inhibit ovarian granulosa cell apoptosis. The mechanism may be associated with upregulation of the PI3K/Akt signaling pathway.

Objective This study aims to assess the impact of four-dimensional cone-beam computed tomography (4D-CBCT) image guidance on setup error correction and target dose distribution optimization in patients receiving stereotactic body radiotherapy for lung cancer. Methods A total of 82 lung cancer patients treated with SBRT in our hospital between February 2023 and February 2025 were randomly selected as study subjects. Using a random number table, they were divided into two groups. The conventional group underwent positioning verification using traditional three-dimensional cone-beam CT, while the study group underwent verification using 4D-CBCT. Setup errors, target dose-volume parameters, organ at risk dose-volume parameters, and adverse reactions were compared between the two groups. Results The setup errors in the X, Y, and Z axes in the study group were 0.21, 0.19, and 0.23 mm, respectively, which were significantly lower than 0.58, 0.62, and 0.59 mm in the conventional group (P<0.05). The three-dimensional vector error was 0.34 (0.21, 0.48) mm in the study group, which was significantly lower than 0.98 (0.65, 1.32) mm in the conventional group (P<0.05). The rotational errors in left-right, anteroposterior, and superior-inferior directions in the study group were (0.25±0.12)°, (0.21±0.10)°, and (0.23±0.11)°, respectively; these values were significantly lower than (0.48±0.18)°, (0.42±0.15)°, and (0.45±0.16)° in the conventional group (P<0.05). The minimum dose received by 95% of the target volume [(59.45±0.85) Gy] and the percentage of the target volume receiving at least 100% of the prescription dose [(95.82±2.65)%] in the study group were higher than those in the conventional group [(58.90±1.20) Gy and (93.65±3.85)%]. The homogeneity index and conformity index in the study group were 1.07±0.03 and 1.15±0.05, respectively, which were lower than 1.12±0.05 and 1.23±0.08 in the conventional group (P<0.05). No significant differences were observed between the two groups in the volume of the lung receiving 5 Gy [(28.11±5.52)% vs. (28.85±6.24)%], the volume of the lung receiving 20 Gy [(12.84±3.56)% vs. (13.45±3.90)%], mean lung dose [(8.65±2.11) Gy vs. (8.95±2.34) Gy], maximum spinal cord dose [(18.54±3.62) Gy vs. (19.13±4.25) Gy], or mean heart dose[(14.85±4.22) Gy vs. (16.27±4.83) Gy](P>0.05). The incidence rates of radiation pneumonitis, radiation esophagitis, and skin reactions in the study group were 12.20%, 7.32%, and 4.88%, respectively, which were not significantly different from 17.07%, 9.76%, and 7.32% in the conventional group (P>0.05). Conclusion The 4D-CBCT can reduce setup errors, improve target dose accuracy and conformity in lung cancer patients undergoing SBRT, and minimize radiation exposure to normal tissues, making it worthy of clinical promotion.

Objective This study aims to assess the impact of four-dimensional cone-beam computed tomography (4D-CBCT) image guidance on setup error correction and target dose distribution optimization in patients receiving stereotactic body radiotherapy for lung cancer. Methods A total of 82 lung cancer patients treated with SBRT in our hospital between February 2023 and February 2025 were randomly selected as study subjects. Using a random number table, they were divided into two groups. The conventional group underwent positioning verification using traditional three-dimensional cone-beam CT, while the study group underwent verification using 4D-CBCT. Setup errors, target dose-volume parameters, organ at risk dose-volume parameters, and adverse reactions were compared between the two groups. Results The setup errors in the X, Y, and Z axes in the study group were 0.21, 0.19, and 0.23 mm, respectively, which were significantly lower than 0.58, 0.62, and 0.59 mm in the conventional group (P<0.05). The three-dimensional vector error was 0.34 (0.21, 0.48) mm in the study group, which was significantly lower than 0.98 (0.65, 1.32) mm in the conventional group (P<0.05). The rotational errors in left-right, anteroposterior, and superior-inferior directions in the study group were (0.25±0.12)°, (0.21±0.10)°, and (0.23±0.11)°, respectively; these values were significantly lower than (0.48±0.18)°, (0.42±0.15)°, and (0.45±0.16)° in the conventional group (P<0.05). The minimum dose received by 95% of the target volume [(59.45±0.85) Gy] and the percentage of the target volume receiving at least 100% of the prescription dose [(95.82±2.65)%] in the study group were higher than those in the conventional group [(58.90±1.20) Gy and (93.65±3.85)%]. The homogeneity index and conformity index in the study group were 1.07±0.03 and 1.15±0.05, respectively, which were lower than 1.12±0.05 and 1.23±0.08 in the conventional group (P<0.05). No significant differences were observed between the two groups in the volume of the lung receiving 5 Gy [(28.11±5.52)% vs. (28.85±6.24)%], the volume of the lung receiving 20 Gy [(12.84±3.56)% vs. (13.45±3.90)%], mean lung dose [(8.65±2.11) Gy vs. (8.95±2.34) Gy], maximum spinal cord dose [(18.54±3.62) Gy vs. (19.13±4.25) Gy], or mean heart dose[(14.85±4.22) Gy vs. (16.27±4.83) Gy](P>0.05). The incidence rates of radiation pneumonitis, radiation esophagitis, and skin reactions in the study group were 12.20%, 7.32%, and 4.88%, respectively, which were not significantly different from 17.07%, 9.76%, and 7.32% in the conventional group (P>0.05). Conclusion The 4D-CBCT can reduce setup errors, improve target dose accuracy and conformity in lung cancer patients undergoing SBRT, and minimize radiation exposure to normal tissues, making it worthy of clinical promotion.

Objective This study aims to assess the impact of four-dimensional cone-beam computed tomography (4D-CBCT) image guidance on setup error correction and target dose distribution optimization in patients receiving stereotactic body radiotherapy for lung cancer. Methods A total of 82 lung cancer patients treated with SBRT in our hospital between February 2023 and February 2025 were randomly selected as study subjects. Using a random number table, they were divided into two groups. The conventional group underwent positioning verification using traditional three-dimensional cone-beam CT, while the study group underwent verification using 4D-CBCT. Setup errors, target dose-volume parameters, organ at risk dose-volume parameters, and adverse reactions were compared between the two groups. Results The setup errors in the X, Y, and Z axes in the study group were 0.21, 0.19, and 0.23 mm, respectively, which were significantly lower than 0.58, 0.62, and 0.59 mm in the conventional group (P<0.05). The three-dimensional vector error was 0.34 (0.21, 0.48) mm in the study group, which was significantly lower than 0.98 (0.65, 1.32) mm in the conventional group (P<0.05). The rotational errors in left-right, anteroposterior, and superior-inferior directions in the study group were (0.25±0.12)°, (0.21±0.10)°, and (0.23±0.11)°, respectively; these values were significantly lower than (0.48±0.18)°, (0.42±0.15)°, and (0.45±0.16)° in the conventional group (P<0.05). The minimum dose received by 95% of the target volume [(59.45±0.85) Gy] and the percentage of the target volume receiving at least 100% of the prescription dose [(95.82±2.65)%] in the study group were higher than those in the conventional group [(58.90±1.20) Gy and (93.65±3.85)%]. The homogeneity index and conformity index in the study group were 1.07±0.03 and 1.15±0.05, respectively, which were lower than 1.12±0.05 and 1.23±0.08 in the conventional group (P<0.05). No significant differences were observed between the two groups in the volume of the lung receiving 5 Gy [(28.11±5.52)% vs. (28.85±6.24)%], the volume of the lung receiving 20 Gy [(12.84±3.56)% vs. (13.45±3.90)%], mean lung dose [(8.65±2.11) Gy vs. (8.95±2.34) Gy], maximum spinal cord dose [(18.54±3.62) Gy vs. (19.13±4.25) Gy], or mean heart dose[(14.85±4.22) Gy vs. (16.27±4.83) Gy](P>0.05). The incidence rates of radiation pneumonitis, radiation esophagitis, and skin reactions in the study group were 12.20%, 7.32%, and 4.88%, respectively, which were not significantly different from 17.07%, 9.76%, and 7.32% in the conventional group (P>0.05). Conclusion The 4D-CBCT can reduce setup errors, improve target dose accuracy and conformity in lung cancer patients undergoing SBRT, and minimize radiation exposure to normal tissues, making it worthy of clinical promotion.

OBJECTIVE T o explore the value of targeted next-generation sequencing(t-NGS)in diagnosis of respir-atory tract pathogens through meta-analysis so as to provide reference for clinical application.METHODS PubMed database,Web of Science database,Wanfang database,CNKI database and Sinomed database were retrieved,and the time period of retrieval ranged from Jan.2010 to May 2024.The literatures were screened out based on the es-tablished standards.The quality was assessed by QU ADAS-2,the risk of bias graph was drawn by Revman 5.4,and the statistical analysis was performed by Stata 16.0.RESULTS A total of 9 literatures were included in the study.The result of meta-analysis showed that the heterogeneity test Q for sensitivity was 268.21,P＜0.01,I2=97.02％,with the heterogeneity test Q for specificity 210.04,P＜0.01,I2=96.19％,the combined sensitivity 0.88(95％CI:0.62 to 0.97),combined specificity 0.68(95％CI:0.41 to 0.86),combined positive likelihood ratio 2.72(95％CI:1.44 to 5.15),combined negative likelihood ratio 0.18(95％CI:0.06 to 0.53),combined diagno-sis score 2.74(95％CI:1.68 to 3.80),and combined diagnostic odds ratio 15.44(95％CI:5.34 to 44.66).The area under synthesize receiver operating characteristic(SROC)curve(AUC)was 0.85(95％CI:0.82 to 0.88).The result of Deeks funnel plot showed that P was 0.99,indicating that there was no obvious publication bias.CONCLUSIONS The sensitivity of tNGS is high in detection of the pathogens causing acute respiratory tract infection,the specificity needs to be improved,but its comprehensive ability is satisfactory.It has certain val-ue in early clinical diagnosis.

Increasing evidence shows that the early lesions of Parkinson's disease (PD) originate from gut, and correction of microbiota dysbiosis is a promising therapy for PD. FLZ is a neuroprotective agent on PD, which has been validated capable of alleviating microbiota dysbiosis in PD mice. However, the detailed mechanisms still need elucidated. Through metabolomics and 16S rRNA analysis, we identified glycoursodeoxycholic acid (GUDCA) was the most affected differential microbial metabolite by FLZ treatment, which was specially and negatively regulated by Clostridium innocuum, a differential microbiota with the strongest correlation to GUDCA production, through inhibiting bile salt hydrolase (BSH) enzyme. The protection of GUDCA on colon and brain were also clarified in PD models, showing that it could activate Nrf2 pathway, further validating that FLZ protected dopaminergic neurons through promoting GUDCA production. Our study uncovered that FLZ improved PD through microbiota-gut-brain axis, and also gave insights into modulation of microbial metabolites may serve as an important strategy for treating PD.

Although enteric glial cell (EGC) abnormal activation is reported to be involved in the pathogenesis of Parkinson's disease (PD), and inhibition of EGC gliosis alleviated gut and dopaminergic neuronal dysfunction was verified in our previous study, the potential role of gut microbiota on EGC function in PD still need to be addressed. In the present study, fecal microbiota transplantation revealed that EGC function was regulated by gut microbiota. By employing 16S rRNA and metabolomic analysis, we identified that 3-indolepropionic acid (IPA) was the most affected differential microbial metabolite that regulated EGC gliosis. The protective effects of IPA on PD were validated in rotenone-stimulated EGCs and rotenone (30 mg/kg i.g. for 4 weeks)-induced PD mice, as indicated by decreased inflammation, improved intestinal and brain barrier as well as dopaminergic neuronal function. Mechanistic study showed that IPA targeted pregnane X receptor (PXR) in EGCs, and inhibition of IL-13Rα1 involved cytokine-cytokine receptor interaction pathway, leading to inactivation of downstream JAK1-STAT6 pathway. Our data not only provided evidence that EGC gliosis was critical in spreading intestinal damage to brain, but also highlighted the potential role of microbial metabolite IPA in alleviating PD pathological damages through gut-brain axis.

[This corrects the article DOI: 10.1016/j.apsb.2025.02.029.].

Objective:To screen the Alzheimer's disease(AD)-related genes and construct its diagnostic model using bioinformatics technology and machine learning(ML)algorithms,to discuss the immunological characteristics of AD patients,and to provide novel biomarkers for AD diagnosis.Methods:The AD-related gene expression dataset GSE125583 was downloaded from the Gene Expression Omnibus(GEO)database.Differentially expressed genes(DEGs)were identified through differential analysis.Gene Ontology(GO)functional enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathway enrichment analyses were performed to explore the biological functions and signaling pathways of DEGs.A protein-protein interaction(PPI)network was constructed,and hub genes were screened using Cytoscape software combined with three ML algorithms:Least Absolute Shrinkage and Selection Operator(LASSO),eXtreme Gradient Boosting(XGBoost),and Random Forest(RF).The screened hub genes were utilized to build an AD diagnostic model via RF,followed by feature importance ranking.The model's efficacy and key genes were evaluated using a test set.Single-sample gene set enrichment analysis(ssGSEA)was used for immune cell infiltration analysis between AD group and control group.Results:Differential analysis identified 1 287 DEGs.The GO functional enrichment analysis results revealed that DEGs were primarily involved in biological functions related to neural signaling,synapses,and vesicles.KEGG signaling pathway enrichment analysis indicated significant enrichment of DEGs in ion transport,neurotransmitter,and ligand-gated channel pathways.Nine overlapping hub genes were screened by the three ML algorithms.In the AD diagnostic model,the top four key genes with highest diagnostic performance were adenylate cyclase-activating polypeptide 1(ADCYAP1),brain-derived neurotrophic factor(BDNF),platelet-derived growth factor receptor β(PDGFRB),and C-X-C motif chemokine receptor 4(CXCR4),with corresponding area under the curve(AUC)values of 0.852,0.795,0.820,and 0.756,respectively.The model achieved an AUC of 0.828,accuracy of 81.25%,sensitivity of 84.40%,and specificity of 71.43%.The immune cell infiltration analysis results demonstrated higher infiltration of macrophages,monocytes,natural killer(NK)cells,and lymphocytes in AD tissue.Among these,NK/natural killer T(NKT)cells and plasmacytoid dendritic cells showed significant correlations with the four key genes(P<0.05).Conclusion:The feature genes screened based on bioinformatics and ML exhibit diagnostic potential for AD.Genes such as ADCYAP1 may serve as potential biomarkers for AD diagnosis,offering significant implications for early prevention and treatment.