Objective To evaluate the predictive ability and clinical application value of artificial intelligence (AI) systems in the benign and malignant differentiation and pathological type of pulmonary nodules, and to summarize clinical application experience. Methods A retrospective analysis was conducted on the clinical data of patients with pulmonary nodules admitted to the Department of Thoracic Surgery, Second Hospital of Lanzhou University, from February 2016 to February 2025. Firstly, pulmonary nodules were divided into benign and non-benign groups, and the discriminative abilities of AI systems and clinicians were compared. Subsequently, lung nodules reported as precursor glandular lesions (PGL), microinvasive adenocarcinoma (MIA), and invasive adenocarcinoma (IAC) in postoperative pathological results were analyzed, comparing the efficacy of AI systems and clinicians in predicting the pathological type of pulmonary nodules. Results In the analysis of benign/non-benign pulmonary nodules, clinical data from a total of 638 patients with pulmonary nodules were included, of which there were 257 males (10 patients and 1 patient of double and triple primary lesions, respectively) and 381 females (18 patients and 1 patient of double and triple primary lesions, respectively), with a median age of 55.0 (47.0, 61.0) years. Different lesions in the same patient were analyzed as independent samples. Univariate analysis of the two groups of variables showed that, except for nodule location, the differences in the remaining variables were statistically significant (P<0.05). Multivariate logistic regression analysis showed that age, nodule type (subsolid pulmonary nodule), average density, spicule sign, and vascular convergence sign were independent influencing factors for non-benign pulmonary nodules, among which age, nodule type (subsolid pulmonary nodule), spicule sign, and vascular convergence sign were positively correlated with non-benign pulmonary nodules, while average density was negatively correlated with the occurrence of non-benign pulmonary nodules. The area under the receiver operating characteristic curve (AUC) of the malignancy risk value given by the AI system in predicting non-benign pulmonary nodules was 0.811, slightly lower than the 0.898 predicted by clinicians. In the PGL/MIA/IAC analysis, clinical data from a total of 411 patients with pulmonary nodules were included, of which there were 149 males (8 patients of double primary lesions) and 262 females (17 patients of double primary lesions), with a median age of 56.0 (50.0, 61.0) years. Different lesions in the same patient were analyzed as independent samples. Univariate analysis results showed that, except for gender, nodule location, and vascular convergence sign, the differences in the remaining variables among the three groups of PGL, MIA, and IAC patients were statistically significant (P<0.05). Multinomial multivariate logistic regression analysis showed that the differences between the parameters in the PGL group and the MIA group were not statistically significant (P>0.05), and the maximum diameter and average density of the nodules were statistically different between the PGL and IAC groups (P<0.05), and were positively correlated with the occurrence of IAC as independent risk factors. The average AUC value, accuracy, recall rate, and F1 score of the AI system in predicting lung nodule pathological type were 0.807, 74.3%, 73.2%, and 68.5%, respectively, all better than the clinical physicians’ prediction of lung nodule pathological type indicators (0.782, 70.9%, 66.2%, and 63.7% respectively). The AUC value of the AI system in predicting IAC was 0.853, and the sensitivity, specificity, and optimal cutoff value were 0.643, 0.943, and 50.0%, respectively. Conclusion This AI system has demonstrated high clinical value in predicting the benign and malignant nature and pathological type of lung nodules, especially in predicting lung nodule pathological type, its ability has surpassed that of clinical physicians. With the optimization of algorithms and the adequate integration of multimodal data, it can better assist clinical physicians in formulating individualized diagnostic and treatment plans for patients with lung nodules.

BACKGROUND: Cluster of differentiation 8 positive (CD8 + ) T cells play a crucial role in the response against tumors, including hepatocellular carcinoma (HCC), where their dysfunction is commonly observed. While the association between elevated peroxisome proliferator-activated receptor alpha (PPARα) expression in HCC cells and exosomes and unfavorable prognosis in HCC patients is well-established, the underlying biological mechanisms by which PPARα induces CD8 + T cell exhaustion mediated by HCC exosomes remain poorly understood. METHODS: Bioinformatics analyses and dual-luciferase reporter assays were used to investigate the regulation of microRNA-27b-3p ( miR-27b-3p ) and thymocyte selection-associated high mobility group box ( Tox ) by Pparα . In vitro and in vivo experiments were conducted to validate the effects of HCC-derived exosomes, miR-27b-3p overexpression, and Pparα on T cell function. Exosome characterization was confirmed using transmission electron microscopy, Western blotting, and particle size analysis. Exosome tracing was performed using small animal in vivo imaging and confocal microscopy. The expression levels of miR-27b-3p , Pparα , and T cell exhaustion-related molecules ( Tox , Havcr2 , and Pdcd1 ) were detected using quantitative reverse transcription polymerase chain reaction analysis, Western blotting analysis, immunofluorescence staining, and flow cytometry analysis. RESULTS: Pparα expression was significantly increased in HCC and negatively correlated with prognosis. It showed a positive correlation with Tox and a negative correlation with miR-27b-3p . The overexpressed Pparα from HCC cells was delivered to CD8 + T cells via exosomes, which absorbed miR-27b-3p both in vitro and in vivo , acting as "miRNA sponges". Further experiments demonstrated that Pparα can inhibit the negative regulation of Tox mediated by miR-27b-3p through binding to its 3'untranslated regions. CONCLUSIONS HCC-derived exosomes deliver Pparα to T cells and promote CD8 + T cell exhaustion and malignant progression of HCC via the miR-27b-3p /TOX regulatory axis. The mechanisms underlying T-cell exhaustion in HCC can be utilized for the advancement of anticancer therapies.
MicroRNAs/metabolism* ; PPAR alpha/genetics* ; Carcinoma, Hepatocellular/genetics* ; Humans ; Liver Neoplasms/genetics* ; CD8-Positive T-Lymphocytes/immunology* ; Exosomes/metabolism* ; Animals ; Cell Line, Tumor ; Mice ; High Mobility Group Proteins/genetics* ; Male ; T-Cell Exhaustion

This article systematically analyzes the historical evolution of the name， origin， medicinal parts， processing and other aspects of Euphorbiae Pekinensis Radix（EPR） by referring to the herbal medicine， medical books， prescription books and other documents of the past dynasties， combined with the relevant modern research materials， so as to provide a basis for the development and utilization of famous classical formulas containing this herbal medicine. According to research， EPR was first recorded in the Shennong Bencaojing in the name of Daji， and it is the correct name of the herbal medicine in all dynasties， there are also other aliases such as Qiongju， Hongya Daji， and Xiamaxian. The dried roots of Euphorbia pekinensis from Euphorbiaceae was the mainstream of the past dynasties. Before the Ming dynasty， the above ground parts of E. pekinensis were used as Zeqi in herbal works. However， since LI Shizhen in the Ming dynasty proposed that the origin of Zeqi should be E. helioscopia， the aerial part of EPR is no longer used as medicine. Since modern times， the roots of Knoxia valerianoides has been used as EPR， and has become the mainstream of commodities， which should be corrected. Throughout history， it has been recorded that the main producing areas were Jiangsu， Anhui， Zhejiang， Shanxi and other regions， while modern botanical survey have shown that EPR is a widespread species distributed throughout the country. In ancient times， the harvesting time of EPR was mostly the twelfth lunar month， while in modern time， it is more common to harvest in autumn and winter. The main processing methods of EPR in ancient times were vinegar processing， wine processing， and stir frying， while in modern times， it is uniformly vinegar processing. In the medicinal properties and clinical aspects， the records are basically consistent throughout history， mainly characterized by bitter taste， cold and toxic nature. Its main efficacy is expelling water retention and reducing swelling. Based on the textual research， it is suggested to choose the dried roots of E. pekinensis when famous classical formulas containing EPR， processing method can be based on the original specified prescription requirements， if the processing method is not clear， it is recommended to use vinegar-processed products as medicine.

Objective To assess potential associations between sarcoma and gut microbiota using Mendelian randomization(MR)analysis.Methods Instrumental variables(IV)for gut microbiota were identified from summary data of a genome-wide association studies(GWAS)involving 18 340 participants from 24 cohorts published by the MiBioGen Consortium.The GWAS on sarcoma from Europe served as an outcome,involving 456 276 sarcoma patients.The inverse-variance weighted(IVW)method was used for primary analysis while sensitivity analysis was made to test the reliability of results of MR analysis.Results IVW results showed that Peptostreptococcaceae(OR=0.353,95％CI 0.127 to 0.979,P=0.045)and Faecalibacterium(OR=0.408,95％CI 0.173 to 0.961,P=0.040)had a negative causal correlation with sarcoma,but the Eubacterium fissicatena group(OR=2.216,95％CI 1.101 to 4.462,P=0.026)and Lachnospiraceae UCG008(OR=1.822,95％CI 1.005 to 3.305,P=0.048)exhibited a positive causal correlation with sarcoma.Sensitivity analysis showed no evidence of pleiotropy and heterogeneity.Conclusion Through two-sample MR,this study identifies a potential causal relationship between four gut microbiota and sarcoma.Peptostreptococcaceae and Faecalibacterium can reduce the risk of sarcoma while the Eubacterium fissicatena group and Lachnospiraceae UCG008 are linked to an increased risk of sarcoma.More research is required to find out more about the way gut microbiota influences the development of sarcoma.

Objective To observe the value of intratumoral tertiary lymphoid structure(TLS)for predicting prognosis of soft tissue sarcomas(STS)after cryoablation combined with immunotherapy.Methods Forty-three STS patients who underwent cryoablation were retrospectively enrolled,including 38 cases underwent cryoablation combined with but 5 cases without immunotherapy,among them 6 cases with but 37 cases without intratumoral TLS.The progression free survival(PFS)were compared between those with and without immunotherapy,as well as those with and without intratumoral TLS.The value of intratumoral TLS for predicting prognosis of STS after cryoablation combined with immunotherapy was analyzed with Cox regression and receiver operating characteristic curves.Results No significant difference of PFS was found between STS patients undwerwent cryoablation combined with and without immunotherapy(P＜0.05).Among 38 cases underwent cryoablation combined with immunotherapy,6 cases were found with but 32 cases without intratumoral TLS,and the median PFS of the former was longer than that of the latter(6 months vs.3 months,P＜0.05).Univariate and multivariate Cox regression analysis revealed that intratumoral TLS and interleukin 2 receptor(IL-R2)were both independent influencing factors of PFS of STS patients after cryoablation combined with immunotherapy(both P＜0.05).The area under the curve(AUC)of intratumoral TLS for predicting PFS of STS patients at 3,6 and 9 months was 0.550,0.577 and 0.699,of IL-R2 was 0.658,0.742 and 0.583,respectively,while of combination of the above two was 0.762,0.787 and 0.881,respectively,all higher than of each intratumoral TLS and IL-R2 alone(all P＜0.05).Conclusion Intratumoral TLS could be used to predict prognosis of STS after cryoablation combined with immunotherapy.Combining with IL-R2 might further improve its predictive efficacy.

Objective To observe the value of intratumoral tertiary lymphoid structure(TLS)for predicting prognosis of soft tissue sarcomas(STS)after cryoablation combined with immunotherapy.Methods Forty-three STS patients who underwent cryoablation were retrospectively enrolled,including 38 cases underwent cryoablation combined with but 5 cases without immunotherapy,among them 6 cases with but 37 cases without intratumoral TLS.The progression free survival(PFS)were compared between those with and without immunotherapy,as well as those with and without intratumoral TLS.The value of intratumoral TLS for predicting prognosis of STS after cryoablation combined with immunotherapy was analyzed with Cox regression and receiver operating characteristic curves.Results No significant difference of PFS was found between STS patients undwerwent cryoablation combined with and without immunotherapy(P＜0.05).Among 38 cases underwent cryoablation combined with immunotherapy,6 cases were found with but 32 cases without intratumoral TLS,and the median PFS of the former was longer than that of the latter(6 months vs.3 months,P＜0.05).Univariate and multivariate Cox regression analysis revealed that intratumoral TLS and interleukin 2 receptor(IL-R2)were both independent influencing factors of PFS of STS patients after cryoablation combined with immunotherapy(both P＜0.05).The area under the curve(AUC)of intratumoral TLS for predicting PFS of STS patients at 3,6 and 9 months was 0.550,0.577 and 0.699,of IL-R2 was 0.658,0.742 and 0.583,respectively,while of combination of the above two was 0.762,0.787 and 0.881,respectively,all higher than of each intratumoral TLS and IL-R2 alone(all P＜0.05).Conclusion Intratumoral TLS could be used to predict prognosis of STS after cryoablation combined with immunotherapy.Combining with IL-R2 might further improve its predictive efficacy.

ObjectiveTo observe the effect of earthworm protein on the expression of phosphatidylinositol 3-kinase/protein kinase B/nuclear factor E₂-related factor 2 （PI3K/Akt/Nrf2） pathway in the aorta of spontaneously hypertensive rats （SHR） and explore mechanism of earthworm protein in treating hypertensive vascular endothelial dysfunction （VED）. MethodTen 10-week-old Wistar Kyoto （WKY） rats and fifty SHR rats were selected for a week of adaptive feeding. WKY rats were selected as the normal group， and fifty SHR rats were randomized according to body weight into model， valsartan （8×10^-3 g·kg^-1·d^-1）， and high-， medium-， and low-dose （0.2， 0.1， 0.05 g·kg^-1·d^-1， respectively） earthworm protein groups. The normal and model groups were administrated with equal volume of double distilled water by gavage. During the drug intervention period， the general situations of rats in each group were observed and their blood pressure was monitored at specific time points every other week before and after administration. After 8 weeks of drug intervention， enzyme-linked immunosorbent assay was employed to measure the levels of angiotensin-Ⅱ （Ang-Ⅱ） and endothelin-1 （ET-1） in the serum of rats in each group. The corresponding kits were used to determine the levels of nitric oxide （NO）， malondialdehyde （MDA）， glutathione peroxidase （GPX）， superoxide dismutase （SOD）， and ferrous ion （Fe²⁺）. Hematoxylin-eosin （HE） staining was employed to observe the changes in the intima of the aorta. Fluorescence quantitative polymerase chain reaction （Real-time PCR） was employed to measure the mRNA levels of PI3K， Akt， Nrf2， heme oxygenase-1 （HO-1）， and glutathione peroxidase 4 （GPX4） in the aortic tissue. Western blotting was used to determine the protein levels of p-PI3K （Tyr467/199）， PI3K， p-Akt （Ser473）， Akt， Nrf2， HO-1， and GPX4 in the thoracic aorta. ResultCompared with the normal group， the model group had decreased body mass， increased irritability， severe endothelial damage， elevated blood pressure and serum levels of Ang-Ⅱ， ET1， MDA， and Fe²⁺ （P<0.01）， lowered NO level （P<0.01）， and down-regulated mRNA and protein levels of p-PI3K （Tyr467/199）， PI3K， p-Akt （Ser473）， Akt， Nrf2， HO-1， and GPX4 in the aortic tissue （P<0.01）. Compared with the model group， drug intervention caused no significant change in the body mass， calmed the rats， alleviated the endothelial damage， lowered blood pressure and serum levels of Ang-Ⅱ， ET1， MDA， and Fe²⁺ （P<0.01）， elevated the NO level （P<0.05）， and up-regulated the mRNA and protein levels of p-PI3K （Tyr467/199）， PI3K， p-Akt （Ser473）， Akt， Nrf2， HO-1， and GPX4 （P<0.05）. ConclusionThe earthworm protein can exert antihypertensive effects by ameliorating VED in SHR. Specifically， it may regulate the PI3K/Akt/Nrf2 signaling pathway to inhibit oxidative stress and ferroptosis.

By consulting ancient materia medica， medical books， prescription books and modern literature， this paper systematically combed and reviewed the name， origin， scientific name evolution， producting area， quality evaluation， medicinal parts， harvesting and processing and traditional efficacy of Lasiosphaera Calvatia. The results show that Mabo was first recorded in Mingyi Bielu. Since then， all dynasties have taken Mabo as a legitimate name. Before the Song dynasty， only Calvatia lilacina was used as the original plant of Lasiosphaera Calvatia， which was expanded after the Song dynasty with the appearance of C. gigantea， Lasiosphaera fenzlii， Bovistella radicata and other varieties. Until modern times， there was an addition of Lycoperdon perlatum， L. pyriforme and other original plants of Lasiosphaera Calvatia. Since 1975， the original plant of Lasiosphaera Calvatia in various regulations and academic monographs has been basically uniform for C. lilacina， Lasiosphaera fenzlii and C. gigantea. Resource of the medicinal fungus was widely distributed in China and was mainly wild. From ancient times to the present， the medicinal parts of Lasiosphaera Calvatia are all fruiting body， which is harvested in summer and autumn， and its processing method was to take powder in ancient times， but to cut blocks in modern times. In recent times， its quality has been summarized as large， thin-skinned， intact， full， loose-bubbled and elastic. The medicinal efficacy has been developed from very good for all scores， and after the Ming and Qing dynasties， it is consistent with the 2020 edition of Chinese Pharmacopoeia， with the efficacy of clearing the lung， promoting pharynx， relieving fever and hemostasis， mainly treating cough aphonia， throat obstruction and pharyngeal pain， vomiting blood， epistaxis， hemoptysis， and external treating sores and bleeding from cuts and wounds. Based on the results of herbal textual research， it is suggested that C. lilacina is the first choice for the origin of Lasiosphaera Calvatia involved in famous classical formulas， and it is processed into block or powder for medicine.

Objective     To investigate the clinical characteristics, risk factors and perioperative outcome of prolonged mechanical ventilation (PMV) in elderly patients undergoing coronary artery bypass grafting (CABG). Methods     The data of elderly patients receiving CABG in the Nanjing First Hospital from January 2013 to June 2019 were collected. All patients were divided into a control group and a PMV group according to whether ventilation time≥24 h. The clinical characteristics and risk factors of PMV were compared between the two groups. Variables were 1∶1 balanced through propensity score matching (PSM) and perioperative outcomes of two groups was analyzed. Results     Finally 956 patients were collected, including 187 in the PMV group and 769 in the control group. There were 586 males and 370 females aged 70-94 (74.3±3.5) years. Compared with the control group, the PMV group had higher rates of smoking,  preoperative renal impairment, intraoperative blood transfusion and intra-aortic balloon pump (IABP) implantation, worse cardiac function, lower glomerular filtration rate and ejection fraction, larger left atrial diameter, longer cardiopulmonary bypass time and aortic cross-clamping time (P<0.05). There was no statistical difference in other clinical data between the two groups (P>0.05). Binary multivariate logistic regression analysis showed that females, smoking, chronic obstructive pulmonary disease, left ventricular ejection fraction≤56.0%, cardiopulmonary bypass time>106.0 min, IABP implantation and intraoperative blood transfusion were independent risk factors for PMV in elderly patients. After PSM, there were 146 patients in the control group and the PMV group, respectively. The PMV group had longer ICU stay and length of hospital stay and more drainage volume compared with the control group (all P<0.05). There was no statistical difference in perioperative mortality or other complications between the two groups (all P>0.05). Conclusion    There are a lot of factors associated with PMV of the elderly patients undergoing on-pump CABG. In order to establish a complete and formal PMV prediction model, clinicians can make a further step of assessment according to perioperative elements, and improve the prognosis of such patients.

Objective To evaluate the effectiveness of the central government-funded echinococcosis control programme in Tianzhu Tibetan Autonomous County, Gansu Province from 2007 to 2022, so as to provide insights into echinococcosis control. Methods Administrative villages were sampled using a multi-stage cluster random sampling method from Tianzhu Tibetan Autonomous County, Gansu Province from 2007 to 2022, and all residents at ages of 12 years and older in the sampled villages were screened for echinococcosis, and schools were sampled using a cluster sampling method, and all children at ages of 12 years and older in the sampled schools were screened for echinococcosis. Domestic dogs were sampled using a systematic random sampling method, and one domestic dog stool sample was collected from each household. Stray dog stool samples were collected outside the villages, and Echinococcus coproantigens were detected using enzyme-linked immunosorbent assay in domestic and stray dogs. In addition, echinococcosis was screened in sheep and cattle in designated slaughterhouses in Tianzhu Tibetan Autonomous County. The trends in the prevalence of echinococcosis in humans and livestock and the positive rate of Echinococcus coproantigens in dogs were examined with the Cochran-Armitage trend test. In addition, individuals screened for echinococcosis were randomly sampled from 2007 to 2022 for survey on the awareness of echinococcosis control knowledge. Results A total of 290 356 person-times were screened for echinococcosis among residents at ages of 12 years and older in Tianzhu Tibetan Autonomous County, Gansu Province from 2007 to 2022, with 1 094 residents detected with cystic echinococcosis, and the detection of echinococcosis appeared a tendency towards a gradual decline over years (χ² = 358.602, P < 0.001). A total of 32 931 person-times were screened for echinococcosis among children at ages of 12 years and older in Tianzhu Tibetan Autonomous County, Gansu Province from 2007 to 2022, with 296 children detected with echinococcosis, and the detection of echinococcosis appeared a tendency towards a gradual decline over years (χ² = 267.673, P < 0.001). A total of 33 230 domestic dog stool samples were tested for Echinococcus coproantigens in Tianzhu Tibetan Autonomous County, Gansu Province from 2007 to 2022, with 1 777 Echinococcus coproantigens-positive samples tested, and the positive rate of Echinococcus coproantigens appeared a tendency towards a decline in domestic dogs over years (χ² = 2 210.428, P < 0.001), while the positive rate of Echinococcus coproantigens showed a tendency towards a rise in domestic animals from 2016 to 2022 (χ² = 37.745, P < 0.001). The positive rate of Echinococcus coproantigens remained relatively stable in stray dogs in Tianzhu Tibetan Autonomous County, Gansu Province from 2019 to 2022 (χ² = 0.315, P = 0.575). A total of 10 973 sheep were screened for echinococcosis in Tianzhu Tibetan Autonomous County from 2007 to 2022, with 334 sheep detected with echinococcosis, and the detection of echinococcosis appeared a tendency towards a decline in sheep over years (χ² = 53.579, P < 0.001); however, there was no significant change in the detection of echinococcosis during the period from 2015 through 2022 (χ² = 1.520, P = 0.218). A total of 2 400 cattle were screened for echinococcosis in Tianzhu Tibetan Autonomous County from 2017 to 2022, with 231 cattle detected with echinococcosis, and the detection of echinococcosis showed a tendency towards a decline over years (χ² = 5.579, P < 0.05). The awareness of echinococcosis control knowledge increased from 44.37% in 2007 to 94.00% in 2022 among residents at ages of 12 years and older and from 52.50% in 2007 to 92.50% in 2022 among children at ages of 12 years and older in Tianzhu Tibetan Autonomous County, respectively. Conclusions There has been a reduction in the detection of echinococcosis in humans and domestic animals and the positive rate of Echinococcus coproantigens in dogs and a rise in the awareness of the echinococcosis control knowledge following the implementation of the central government-funded echinococcosis control programme in Tianzhu Tibetan Autonomous County, Gansu Province; however, integrated echinococcosis control measures are still required for further control of the prevalence of echinococcosis.