Objective:To investigate the impact of different etiologies on the spatial distribution pattern of infarcts and the mapping pattern of focal symptoms in acute ischemic stroke (AIS) using a population-based standardized spatial analysis of MRI.Methods:This was a cross-sectional study. Clinical [age, sex distribution, admission National Institutes of Health Stroke Scale (NIHSS) score and 90-day modified Rankin Scale (mRS) score at discharge, etc.] and imaging data of 2 610 patients with AIS attending 9 Medical Centers from January 2015 to December 2021 were retrospectively analyzed. All patients were categorized into 1 718 cases of large artery atherosclerosis (LAA) type, 335 cases of cardioembolism (CE) type, and 557 cases of small artery occlusion (SAO) type according to TOAST typing. All patients underwent diffusion-weighted imaging, and the detected infarct lesions were segmented and aligned to the standardized space using artificial intelligence-assisted methods, and the spatial distribution frequency heatmaps of lesion locations in patients with different TOAST subtypes were plotted and compared with each other by χ2 test. Lesion-symptom image brain maps with different clinical symptoms were further plotted, and differences of lesion-symptom image relationships among different TOAST subtypes were observed and compared with each other by interaction effect. Results:In all patients, the favored sites of infarct lesions were the bilateral middle cerebral artery region in the anterior circulation and the occipital and brainstem regions in the posterior circulation. Compared with the LAA type, the CE type lesions were more likely to occur in the anterior cerebral artery region, the occipital lobe, and the cerebellum posterior, while the SAO type lesions were more likely to occur in the perforator artery supply area. The lesion-symptom mapping results showed that AIS patients with infarct lesions in the frontoparieto-temporal region in the presence of a left middle cerebral artery supply had higher admission NIHSS scores and higher discharge 90-day mRS scores for the LAA type than for the CE type( P<0.05); AIS patients with infarcted lesions in the brainstem region and some cerebellar regions in the presence of vertebrobasilar artery supply had higher admission NIHSS scores and higher discharge 90-day mRS scores for the CE type than for the LAA type( P<0.05). Conclusion:At the population level, brain mapping reveals specific infarct distribution patterns and differences in lesion-symptom mapping patterns of different etiologies AIS patients, providing imaging evidence for the understanding of AIS pathogenetic mechanisms and clinical management.

Objective To explore the application value of CT-based radiomics in differentiating pneumonia-type mucinous adenocarcinoma(PTMA)from organizing pneumonia(OP).Methods A total of 52 PTMA patients and 102 OP patients were retrospectively included and randomly divided into training set(n=124)and test set(n=30)in an 8∶2 ratio.Eight PTMA patients and 22 OP patients from another hospital during the same period were included as external validation set(n=30).Clinical characteristics and CT signs of the patients were selected to construct the clinical model.Radiomics features were extracted and dimensionality reduction was performed through the least absolute shrinkage and selection operator(LASSO)algorithm.A radiomics model was constructed and the Radiomics score(Radscore)was calculated.The Radscore was combined with clinical factors to establish the combined model and a nomogram was illustrated.The models' fitting degree was analyzed by the calibration curve,while their efficacy was evaluated by the receiver operating characteristic(ROC)curve and decision curve analysis(DCA).Results The clinical model,established based on the border,cystic space and bronchial leafless tree sign,achieved area under the curve(AUC)of 0.850,0.782,and 0.759 in the training set,test set,and external validation set,respectively.Thirteen features were obtained to construct the radiomics model,with AUC of 0.925,0.865,and 0.830,respectively.The AUC of the combined model were 0.970,0.905,and 0.864,respectively,in which the calibration curve demonstrated good model fitting.DCA indicated that the combined model had the greatest clinical net benefit.Conclusion The combined model based on CT radiomics can effectively distinguish PTMA from OP.

Objective To explore the application value of CT-based radiomics in differentiating pneumonia-type mucinous adenocarcinoma(PTMA)from organizing pneumonia(OP).Methods A total of 52 PTMA patients and 102 OP patients were retrospectively included and randomly divided into training set(n=124)and test set(n=30)in an 8∶2 ratio.Eight PTMA patients and 22 OP patients from another hospital during the same period were included as external validation set(n=30).Clinical characteristics and CT signs of the patients were selected to construct the clinical model.Radiomics features were extracted and dimensionality reduction was performed through the least absolute shrinkage and selection operator(LASSO)algorithm.A radiomics model was constructed and the Radiomics score(Radscore)was calculated.The Radscore was combined with clinical factors to establish the combined model and a nomogram was illustrated.The models' fitting degree was analyzed by the calibration curve,while their efficacy was evaluated by the receiver operating characteristic(ROC)curve and decision curve analysis(DCA).Results The clinical model,established based on the border,cystic space and bronchial leafless tree sign,achieved area under the curve(AUC)of 0.850,0.782,and 0.759 in the training set,test set,and external validation set,respectively.Thirteen features were obtained to construct the radiomics model,with AUC of 0.925,0.865,and 0.830,respectively.The AUC of the combined model were 0.970,0.905,and 0.864,respectively,in which the calibration curve demonstrated good model fitting.DCA indicated that the combined model had the greatest clinical net benefit.Conclusion The combined model based on CT radiomics can effectively distinguish PTMA from OP.

Objective To investigate the preventive efficacy of recombinant human granulocyte-macrophage colony-stimulating factor(rhGM-CSF)combined with Kangfuxin liquid on radiation dermatitis in breast cancer patients underwent radiotherapy.Methods A total of 90 breast cancer patients were randomized into the control group(45 cases,rhGM-CSF alone)and the observation group(45 cases,rhGM-CSF+Kangfuxin liquid).Both groups received radiotherapy.The incidence of radiation dermatitis,the time of first occurrence,the healing time and severity of radiation dermatitis(graded by RTOG criteria)were compared between the two groups.Skin growth factors[epidermal growth factor(EGF),basic fibroblast growth factor(bFGF),transforming growth factor-β(TGF-β)]were measured via enzyme linked immunosorbent assay(ELISA)before radiotherapy and 2 weeks after radiotherapy.The quality of life of patients was assessed using the EORTC QLQ-C30 V3.0 questionnaire.Results The incidence of radiation dermatitis was significantly lower in the observation group(35.56%,16/45)than that in the control group(68.89%,31/45,P＜0.05),and the first occurrence time of dermatitis was later,the healing time was shorter,and the severity grade of dermatitis was lower(P＜0.05).Two weeks after radiotherapy,levels of EGF,bFGF,TGF-β and the scores of QLQ-C30 increased in both groups,and those of the observation group were significantly higher than the control group(P＜0.05).Conclusion Combining rhGM-CSF with Kangfuxin liquid can effectively prevent radiation dermatitis in breast cancer patients by reducing incidence and severity,delaying onset time,accelerating healing,and improving quality of life.

Objective To compare the dosimetric differences between volumetric modulated arc therapy(VMAT)and intensity modulated radiation therapy(IMRT)in the irradiation of chest wall and upper and lower clavicle regions after radical mastectomy for breast cancer.Methods A total of 100 patients who were scheduled to receive radiotherapy after radical mastectomy were included and selected as research subjects.Patients were divided into the VMAT group and the IMRT group by random number table method,with 50 cases in each group.The target dose parameters,exposure dose of organs at risk,monitor unit(MU)and treatment time were compared between the two groups.Results There were no statistical differences in V95 and V110 between the VMAT group and the IMRT group(P＞0.05).The D2%in the VMAT group was lower than that of the IMRT group,while D98%and D50%were higher in the VMAT group than those in the IMRT group(P＜0.05).Target area uniformity and target area conformity were better in the VMAT group than those in the IMRT group(P＜0.05).There were no significant differences in mean cardiac dose(Dmean)and ipsilateral lung V5 and V10 between the VMAT group and the IMRT group(P＞0.05).The heart V20 and V30,contralateral lung Dmean,maximum spinal cord dose(Dmax),contralateral breast Dmean,ipsilateral lung Dmean,V20,V30 and mean MU were lower in the VMAT group than those in the IMRT group,and the treatment time was shorter than that in the IMRT group(P＜0.05).Conclusion In the irradiation treatment of chest wall and upper and lower clavicle regions after radical mastectomy,VMAT demonstrates superior dosimetric characteristics and higher treatment efficiency compared with IMRT,particularly in terms of target area uniformity,target area conformity and exposure doses to organs at risk.

Objective:To evaluate the role of interferon regulatory factor 3 (IRF3) in renal fibrosis in a mouse model of renal ischemia-reperfusion injury.Methods:Twelve male C57BL/6J wild-type mice and 12 macrophage IRF3 conditional knockout C57BL/6J mice, aged 8-10 weeks, weighing 20-25 g, were divided into 2 groups ( n=6 each) using a random number table method: wild-type sham operation group (WT-Sham group) and wild-type renal ischemia-reperfusion injury group (WT-I/R group); IRF3 conditional knockout sham operation group (cKO-Sham group) and IRF3 conditional knockout I/R group (cKO-I/R group). The model of renal I/R injury was established by occluding bilateral renal pedicles for 45 min followed by reperfusion in anesthetized animals. The orbital blood samples and renal tissues were collected at 14 days of reperfusion for determination of the concentrations of blood urea nitrogen (BUN) and creatinine (Cr) in serum, expression of fibronectin, collagen-I, alpha-smooth muscle actin (α-SMA) (by immunofluorescence), F4/80-α-SMA double positive cell count, and mRNA expression of interleukin-6 (IL-6), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) and transforming growth factor-β1 (TGF-β1) in renal tissues (by real-time polymerase chain reaction) and for observation of pathological changes which were scored. The area of renal fibrosis was measured. Results:For two types of mice, compared with group Sham, the levels of serum BUN and Cr, area of renal fibrosis and renal injury score were significantly increased, the expression of fibronectin, COL-Ⅰ and α-SMA protein and IL-6, IL-1β, TNF-α and TGF-β1 mRNA was up-regulated, and the F4/80-α-SMA dual positive cell count was increased in group WT-I/R ( P<0.05). Compared with group WT-I/R, the concentrations of BUN and Cr in serum, area of renal fibrosis and renal injury score were significantly decreased, the expression of fibronectin, COL-Ⅰ and α-SMA protein and IL-6, IL-1β, TNF-α and TGF-β1 mRNA was down-regulated, and the F4/80-α-SMA dual positive cell count was decreased in cKO-I/R group ( P<0.05). Conclusions:IRF3 is involved in the process of renal fibrosis in a mouse model of renal ischemia-reperfusion injury, and the mechanism may be associated with the promotion of inflammatory responses and the transformation of macrophages into myofibroblasts.

Objective To compare the dosimetric differences between volumetric modulated arc therapy(VMAT)and intensity modulated radiation therapy(IMRT)in the irradiation of chest wall and upper and lower clavicle regions after radical mastectomy for breast cancer.Methods A total of 100 patients who were scheduled to receive radiotherapy after radical mastectomy were included and selected as research subjects.Patients were divided into the VMAT group and the IMRT group by random number table method,with 50 cases in each group.The target dose parameters,exposure dose of organs at risk,monitor unit(MU)and treatment time were compared between the two groups.Results There were no statistical differences in V95 and V110 between the VMAT group and the IMRT group(P＞0.05).The D2%in the VMAT group was lower than that of the IMRT group,while D98%and D50%were higher in the VMAT group than those in the IMRT group(P＜0.05).Target area uniformity and target area conformity were better in the VMAT group than those in the IMRT group(P＜0.05).There were no significant differences in mean cardiac dose(Dmean)and ipsilateral lung V5 and V10 between the VMAT group and the IMRT group(P＞0.05).The heart V20 and V30,contralateral lung Dmean,maximum spinal cord dose(Dmax),contralateral breast Dmean,ipsilateral lung Dmean,V20,V30 and mean MU were lower in the VMAT group than those in the IMRT group,and the treatment time was shorter than that in the IMRT group(P＜0.05).Conclusion In the irradiation treatment of chest wall and upper and lower clavicle regions after radical mastectomy,VMAT demonstrates superior dosimetric characteristics and higher treatment efficiency compared with IMRT,particularly in terms of target area uniformity,target area conformity and exposure doses to organs at risk.

Objective To explore the potential targets and mechanism of Gufang Granules in treating osteoporosis through network pharmacology,molecular dynamics simulations,and in vitro experiment validation.Methods The active components of Gufang Granules were obtained from the TCMSP database and literature,and their related targets were predicted using SwissTargetPrediction database.Core drug targets were selected through protein-protein interaction(PPI)network analysis and machine learning models,and the predictive performance of the models was assessed by drawing receiver operating characteristic(ROC)curves on independent validation datasets.Gene Set Enrichment Analysis(GSEA)was used to analyze the expression and pathways of core targets.Molecular dynamics(MD)simulations were applied to evaluate the structural stability and interactions of the compound-target complexes.Non-cytotoxic concentrations of Gufang Granules containing serum were determined by the CCK-8 assay.RAW264.7 cells were treated with low,medium,and high concentrations of drug containing serum,respectively.The number of osteoclasts was quantified using TRAP staining.The expression levels of relevant genes and proteins were analyzed through qRT-PCR and Western blot methods.Results A total of 251 potential active components and 1 078 related targets of Gufang Granules were identified.The high expressions of core targets SRC and TNF were mainly associated with osteoclast differentiation,MAPK signaling pathway and PI3K/Akt signaling pathway.MD simulations showed that the core active component Glabridin exhibited strong stability and interaction with the SRC and TNF target proteins.The number of TRAP positive cells in all concentration groups of Gufang Granules was significantly reduced compared to the RANKL group(P<0.01,P<0.001).The serum containing Gufang Granules significantly reduced the mRNA expression of NFATc1,CTSK,SRC and TNF-α,and also downregulated the protein expression of NFATc1,CTSK,p-SRC and TNF-α(P<0.05,P<0.01,P<0.001).Conclusion Gufang Granules may inhibit osteoclast differentiation by downregulating the expression of NFATc1,CTSK,p-SRC and TNF-α,thereby slowing the pathological progression of osteoporosis.

Objective To investigate the preventive efficacy of recombinant human granulocyte-macrophage colony-stimulating factor(rhGM-CSF)combined with Kangfuxin liquid on radiation dermatitis in breast cancer patients underwent radiotherapy.Methods A total of 90 breast cancer patients were randomized into the control group(45 cases,rhGM-CSF alone)and the observation group(45 cases,rhGM-CSF+Kangfuxin liquid).Both groups received radiotherapy.The incidence of radiation dermatitis,the time of first occurrence,the healing time and severity of radiation dermatitis(graded by RTOG criteria)were compared between the two groups.Skin growth factors[epidermal growth factor(EGF),basic fibroblast growth factor(bFGF),transforming growth factor-β(TGF-β)]were measured via enzyme linked immunosorbent assay(ELISA)before radiotherapy and 2 weeks after radiotherapy.The quality of life of patients was assessed using the EORTC QLQ-C30 V3.0 questionnaire.Results The incidence of radiation dermatitis was significantly lower in the observation group(35.56%,16/45)than that in the control group(68.89%,31/45,P＜0.05),and the first occurrence time of dermatitis was later,the healing time was shorter,and the severity grade of dermatitis was lower(P＜0.05).Two weeks after radiotherapy,levels of EGF,bFGF,TGF-β and the scores of QLQ-C30 increased in both groups,and those of the observation group were significantly higher than the control group(P＜0.05).Conclusion Combining rhGM-CSF with Kangfuxin liquid can effectively prevent radiation dermatitis in breast cancer patients by reducing incidence and severity,delaying onset time,accelerating healing,and improving quality of life.

Peganum harmala L. (P. harmala) is a significant economic and medicinal plant. The seeds of P. harmala have been extensively utilized in traditional Chinese medicine, Uighur medicine, and Mongolian medicine, as documented in the Drug Standard of the Ministry of Health of China. Twelve novel tryptamine-derived alkaloids (1-12) and eight known compounds (13-20) were isolated from P. harmala seeds. Compounds 1 and 2 represent the first reported instances of tryptamine-derived heteromers, comprising tryptamine and aniline fragments with previously undocumented C-3-N-1' linkage and C-3-C-4' connection, respectively. Compounds 3-5 were identified as indole-quinazoline heteromers, exhibiting a novel C-3 and NH-1' linkage between indole and quinazoline-derived fragments. Compound 6 demonstrates the dimerization pattern of C-C linked tryptamine-quinazoline dimer. Compound 8 represents a tryptamine-derived heterodimer with a distinctive carbon skeleton, featuring an unusual spiro-tricyclic ring (7) and conventional bicyclic tryptamine. Compounds 9-11 constitute novel 6/5/5/5 spiro-tetracyclic tryptamine-derived alkaloids presenting a unique ring system of tryptamine-spiro-pyrrolizine. Compounds 1-3 and 6-11 were identified as racemates. Compounds 2, 7, 9, 10, and 12 were confirmed via X-ray crystallographic analysis. All isolated compounds (1-20) exhibited varying degrees of antiviral efficacy against respiratory syncytial virus (RSV). Notably, the anti-RSV activity of compound 12 (IC₅₀ 5.01 ± 0.14 μmol·L^-1) surpassed that of the positive control (ribavirin, IC₅₀ 6.23 ± 0.95 μmol·L^-1), as validated through plaque reduction and immunofluorescence assays. The identification of anti-RSV compounds from P. harmala seeds may enhance the development and application of this plant in antiviral therapeutic products.
Antiviral Agents/isolation & purification* ; Tryptamines/isolation & purification* ; Peganum/chemistry* ; Seeds/chemistry* ; Alkaloids/isolation & purification* ; Molecular Structure ; Humans ; Respiratory Syncytial Viruses/drug effects* ; Plant Extracts/pharmacology* ; Drugs, Chinese Herbal/pharmacology*