Objective To establish and internally validate a predictive model for poorly differentiated adenocarcinoma based on CT imaging and tumor marker results. Methods Patients with solid and partially solid lung nodules who underwent lung nodule surgery at the Department of Thoracic Surgery, the Affiliated Brain Hospital of Nanjing Medical University in 2023 were selected and randomly divided into a training set and a validation set at a ratio of 7:3. Patients' CT features, including average density value, maximum diameter, pleural indentation sign, and bronchial inflation sign, as well as patient tumor marker results, were collected. Based on postoperative pathological results, patients were divided into a poorly differentiated adenocarcinoma group and a non-poorly differentiated adenocarcinoma group. Univariate analysis and logistic regression analysis were performed on the training set to establish the predictive model. The receiver operating characteristic (ROC) curve was used to evaluate the model's discriminability, the calibration curve to assess the model's consistency, and the decision curve to evaluate the clinical value of the model, which was then validated in the validation set. Results A total of 299 patients were included, with 103 males and 196 females, with a median age of 57.00 (51.00, 67.25) years. There were 211 patients in the training set and 88 patients in the validation set. Multivariate analysis showed that carcinoembryonic antigen (CEA) value [OR=1.476, 95%CI (1.184, 1.983), P=0.002], cytokeratin 19 fragment antigen (CYFRA21-1) value [OR=1.388, 95%CI (1.084, 1.993), P=0.035], maximum tumor diameter [OR=6.233, 95%CI (1.069, 15.415), P=0.017], and average density [OR=1.083, 95%CI (1.020, 1.194), P=0.040] were independent risk factors for solid and partially solid lung nodules as poorly differentiated adenocarcinoma. Based on this, a predictive model was constructed with an area under the ROC curve of 0.896 [95%CI (0.810, 0.982)], a maximum Youden index corresponding cut-off value of 0.103, sensitivity of 0.750, and specificity of 0.936. Using the Bootstrap method for 1000 samplings, the calibration curve predicted probability was consistent with actual risk. Decision curve analysis indicated positive benefits across all prediction probabilities, demonstrating good clinical value. Conclusion For patients with solid and partially solid lung nodules, preoperative use of CT to measure tumor average density value and maximum diameter, combined with tumor markers CEA and CYFRA21-1 values, can effectively predict whether it is poorly differentiated adenocarcinoma, allowing for early intervention.

OBJECTIVE To optimize the management model of drugs used in investigator-initiated trial （IIT）. METHODS With benchmarking analysis， based on the practical work experience of a tertiary specialized hospital in the field of IIT drug management in Shanghai， a thorough review was conducted， involving relevant laws， regulations， and academic literature to establish benchmark criteria and the evaluation standards. Starting from the initiation of IIT projects， a detailed comparative analysis of key processes was carried out， such as the receipt， storage， distribution， use and recycling of drugs for trial. The deficiencies in the current management of IIT drugs were reviewed in detail and a series of optimization suggestions were put forward. RESULTS It was found that the authorized records of drug management were missing， the training before project implementation was insufficient， and the records of receipt and acceptance of IIT drugs were incomplete. In light of these existing problems， improvement measures were put forward， including strengthening the training of drug administrators and stipulating that only drug administrators with pharmacist qualifications be eligible to inspect and accept drugs， etc. The related systems were improved， and 17 key points of quality control for the management of IIT drugs were developed. CONCLUSIONS A preliminary IIT drug management system for medical institutions has been established， which helps to improve the institutional X2023076） framework of medical institutions in this field.

Objective To investigate the setup error in patients with spinal bone metastasis who underwent radiotherapy under the guidance of kilovoltage cone-beam CT (KV-CBCT). Methods A total of 118 patients with spinal metastasis who underwent radiotherapy, including 17 cases of cervical spine, 62 cases of thoracic spine, and 39 cases of lumbar spine, were collected. KV-CBCT scans were performed using the linear accelerators from Elekta and Varian’s EDGE system. CBCT images were registered with reference CT images in the bone window mode. A total of 973 data were collected, and 3D linear errors were recorded. Results The patients with spinal bone metastasis were grouped by site, height, weight, and BMI. The P value of the patients grouped only by site was P<0.05, which was statistically significant. Conclusion When grouped by site in the 3D direction, the positioning effect of cervical spine is better than that of thoracic and lumbar spine. The positioning effect of the thoracic spine is better in the head and foot direction but worse in the left and right direction compared with that of the lumbar spine. Instead of extending or narrowing the margin according to the BMI of patients with spinal metastasis, the margin must be changed according to the site of spinal bone metastasis.

Threatened abortion is a common disease of obstetrics and gynecology and one of the diseases responding specifically to traditional Chinese medicine （TCM）. The China Association of Chinese Medicine organized experts in TCM obstetrics and gynecology， Western medicine obstetrics and gynecology， and pharmacology to deeply discuss the advantages of TCM and integrated Chinese and Western medicine treatment as well as the medication plans for threatened abortion. After discussion， the experts concluded that chromosome， endocrine， and immune abnormalities were the key factors for the occurrence of threatened abortion， and the Qi and blood disorders in thoroughfare and conception vessels were the core pathogenesis. In the treatment of threatened abortion， TCM has advantages in preventing miscarriages， alleviating clinical symptoms and TCM syndromes， relieving anxiety， regulating reproductive endocrine and immune abnormalities， personalized and diversified treatment， enhancing efficiency and reducing toxicity， and preventing the disease before occurrence. The difficulty in diagnosis and treatment of threatened abortion with traditional Chinese and Western medicine lies in identifying the predictors of abortion caused by maternal factors and the treatment of thrombophilia. Recurrent abortion is the breakthrough point of treatment with integrated traditional Chinese and Western medicine. It is urgent to carry out high-quality evidence-based medicine research in the future to improve the modern diagnosis and treatment of threatened abortion with TCM.

Diabetic osteoporosis （DOP） is a kind of bone complication caused by diabetes， which is characterized by the decrease of bone mineral density， the change of bone microstructure and the increase of bone fragility. The process of DOP is closely related to high glucose， insulin resistance， oxidative stress and other mechanisms. The Wnt/β-catenin signaling pathway plays an important role in mediating insulin resistance and bone metabolic balance in diabetes. Regulation of Wnt signal transduction promotes the expression of glycogen synthase kinase-3β（GSK-3β）phosphorylation and improves glucose and lipid metabolism. The Wnt/β-catenin signaling pathway is also an important way regulating osteocyte-driven bone remodeling， which not only plays an important regulatory role in the balance between osteoblasts and osteoclasts and improve bone metabolic homeostasis， but also promotes the expression of osteopontin， osteocalcin and type Ⅰ collagen， and improves bone proliferation and osteogenic differentiation by regulating the Wnt pathway. In recent years， the research of traditional Chinese medicine （TCM） in the prevention and treatment of DOP has gradually increased， and the exploration of TCM to interfere with the Wnt pathway to improve DOP has made some progress. This paper collects and summarizes the studies on the Wnt signaling pathway in glucose metabolism， bone metabolism and DOP worldwide in the past decade， as well as the related literature on the intervention of DOP by TCM compounds （classical and other compounds）， single Chinese medicine and TCM monomers based on the Wnt pathway， in order to provide a reference and direction for the development of new drugs for clinical prevention and treatment of DOP.

Idiopathic pulmonary fibrosis （IPF）， as a progressive lung disease， has a poor prognosis and no reliable and effective therapies. IPF is mainly treated by organ transplantation and administration of chemical drugs， which are ineffective and induce side effects， failing to meet the clinical needs. Therefore， developing safer and more effective drugs has become an urgent task， which necessitates clear understanding of the pathogenesis of IPF. The available studies about the pathogenesis of IPF mainly focus on macrophage polarization， epithelial-mesenchymal transition （EMT）， oxidative stress， and autophagy， while few studies systematically explain the principles and links of the pathogeneses. According to the traditional Chinese medicine theory， Qi deficiency and blood stasis and Qi-Yang deficiency are the key pathogeneses of IPF. Therefore， the Chinese medicines or compound prescriptions with the effects of replenishing Qi and activating blood， warming Yang and tonifying Qi， and eliminating stasis and resolving phlegm are often used to treat IPF. Modern pharmacological studies have shown that such medicines play a positive role in inhibiting macrophage polarization， restoring redox balance， inhibiting EMT， and regulating cell autophagy. However， few studies report how Chinese medicines regulate the pathways in the treatment of IPF. By reviewing the latest articles in this field， we elaborate on the pathogenesis of IPF and provide a comprehensive overview of the mechanism of the active ingredients or compound prescriptions of Chinese medicines in regulating IPF. Combining the pathogenesis of IPF with the modulating effects of Chinese medicines， we focus on exploring systemic treatment options for IPF， with a view to providing new ideas for the in-depth study of IPF and the research and development of related drugs.

Twelve compounds were isolated from the ethyl acetate fraction of the 80% aqueous ethanol extract of the roots and stems of Dalbergia rimosa Roxb. by silica gel, MCI, Sephadex LH-20 column chromatography, and semi-preparative HPLC. Their structures were identified by spectral analysis such as UV, IR, MS, 1D/2D NMR and by comparison with literature information as dalbergiquinol A (1), dalbergiquinol B (2), R-(-)-3′-hydroxy-2,4,5-trimethoxydalbergiquinol (3), neokhriol A (4), mucronulatol (5), (3R)-7,2′,3′-trihydroxy-4′-methoxy-isoflavane (6), isomucronulatol (7), (3S)-violanone (8), 3′-O-methylviolanone (9), eryvarin M (10), (±)-α,3,4,2′,4′-pentahydroxydihydrochalcone (11) and (-)-butin (12). Compound 1 and 2 are new compounds, and compounds 3-12 were isolated from this plant for the first time. Compounds 1, 2, 4, 6, 8, 11, 12 showed good scavenging effect on DPPH free radical.

ObjectiveHuman Ku70 protein mainly involves the non-homologous end joining (NHEJ) repair of double-stranded DNA breaks (DSB) through its DNA-binding properties, and it is recently reported having an RNA-binding ability. This paper is to explore whether Ku70 has RNA helicase activity and affects miRNA maturation. MethodsRNAs bound to Ku protein were analyzed by RNA immunoprecipitation sequencing (RIP-seq) and bioinfomatic anaylsis. The expression relationship between Ku protein and miRNAs was verified by Western blot (WB) and quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) assays. Binding ability of Ku protein to the RNAs was tested by biolayer interferometry (BLI) assay. RNA helicase activity of Ku protein was identified with EMSA assay. The effect of Ku70 regulated miR-124 on neuronal differentiation was performed by morphology analysis, WB and immunofluorescence assays with or without Zika virus (ZIKV) infection. ResultsWe revealed that the Ku70 protein had RNA helicase activity and affected miRNA maturation. Deficiency of Ku70 led to the up-regulation of a large number of mature miRNAs, especially neuronal specific miRNAs like miR-124. The knockdown of Ku70 promoted neuronal differentiation in human neural progenitor cells (hNPCs) and SH-SY5Y cells by boosting miR-124 maturation. Importantly, ZIKV infection reduced the expression of Ku70 whereas increased expression of miR-124 in hNPCs, and led to morphologically neuronal differentiation. ConclusionOur study revealed a novel function of Ku70 as an RNA helicase and regulating miRNA maturation. The reduced expression of Ku70 with ZIKV infection increased the expression of miR-124 and led to the premature differentiation of embryonic neural progenitor cells, which might be one of the causes of microcephaly.

Objective:To observe and verify the changes of transcriptome in hyperoxia-induced acute lung injury (HALI), and to further clarify the changes of pathways in HALI.Methods:Twelve healthy male C57BL/6J mice were randomly divided into normoxia group and HALI group according to the random number table, with 6 mice in each group. The mice in the normoxia group were fed normally in the room, and the mice in the HALI group was exposed to 95% oxygen to reproduce the HALI animal model. After 72 hours of hyperoxia exposure, the lung tissues were taken for transcriptome sequencing, and then Kyoto Encyclopedia of Genes and Genomes database (KEGG) pathway enrichment analysis was performed. The pathological changes of lung tissue were observed under light microscope after hematoxylin-eosin (HE) staining. Real-time fluorescence quantitative reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting were used to verify the key molecules in the signal pathways closely related to HALI identified by transcriptomics analysis.Results:Transcriptomic analysis showed that hyperoxia induced 537 differentially expressed genes in lung tissue of mice as compared with the normoxia group including 239 up-regulated genes and 298 down-regulated genes. Further KEGG pathway enrichment analysis identified 20 most significantly enriched pathway entries, and the top three pathways were ferroptosis signaling pathway, p53 signaling pathway and glutathione (GSH) metabolism signaling pathway. The related genes in the ferroptosis signaling pathway included the up-regulated gene heme oxygenase-1 (HO-1) and the down-regulated gene solute carrier family 7 member 11 (SLC7A11). The related genes in the p53 signaling pathway included the up-regulated gene tumor suppressor gene p53 and the down-regulated gene murine double minute 2 (MDM2). The related gene in the GSH metabolic signaling pathway was up-regulated gene glutaredoxin 1 (Grx1). The light microscope showed that the pulmonary alveolar structure of the normoxia group was normal. In the HALI group, the pulmonary alveolar septum widened and thickened, and the alveolar cavity shrank or disappeared. RT-RCR and Western blotting confirmed that compared with the normoxia group, the mRNA and protein expressions of HO-1 and p53 in lung tissue of the HALI group were significantly increased [HO-1 mRNA (2 -ΔΔCt): 2.16±0.17 vs. 1.00±0.00, HO-1 protein (HO-1/β-actin): 1.05±0.01 vs. 0.79±0.01, p53 mRNA (2 -ΔΔCt): 2.52±0.13 vs. 1.00±0.00, p53 protein (p53/β-actin): 1.12±0.02 vs. 0.58±0.03, all P < 0.05], and the mRNA and protein expressions of Grx1, MDM2, SLC7A11 were significantly decreased [Grx1 mRNA (2 -ΔΔCt): 0.53±0.05 vs. 1.00±0.00, Grx1 protein (Grx1/β-actin): 0.54±0.03 vs. 0.93±0.01, MDM2 mRNA (2 -ΔΔCt): 0.48±0.03 vs. 1.00±0.00, MDM2 protein (MDM2/β-actin): 0.57±0.02 vs. 1.05±0.01, SLC7A11 mRNA (2 -ΔΔCt): 0.50±0.06 vs. 1.00±0.00, SLC7A11 protein (SLC7A11/β-actin): 0.72±0.03 vs. 0.98±0.01, all P < 0.05]. Conclusions:HALI is closely related to ferroptosis, p53 and GSH metabolism signaling pathways. Targeting the key targets in ferroptosis, p53 and GSH metabolism signaling pathways may be an important strategy for the prevention and treatment of HALI.

Objective:To investigate the application of 3.0T high resolution magnetic resonance imaging(HR-MRI)in acute ischemic stroke(AIS)and the influence factors of prognosis.Methods:A total of 92 AIS patients who underwent treatment in Hainan General Hospital from January 2019 to June 2022 were selected as the research objects.All patients were treated by thrombolytic therapy,and they were divided into favorable prognosis group(mRS scores≤2 points,n=66)and poor prognosis group(mRS score>2 points,n=26)according to modified Rankin Scale after they received 90d treatment.All of patients underwent Magnetom Trio type of 3.0 T HR-MRI examination within 1 week after they hospitalized,and the changes of luminal stenosis rate,the luminal area at the narrowest point,the plaque load,T2WIsignal intensity index,T1WI signal intensity index,plaque enhancement rate and other parameters were compared.The receiver operating characteristics(ROC)curve was adopted to analyze the predictive value of 3.0T HR-MRI parameters on the AIS prognosis.Binary Logistic regression model was used to analyze the risk factors that affected the prognosis of AIS patients.Results:The difference of infarction diameter between two groups was statistically significant(x2=6.574,P<0.05).The lumen area at the narrowest point in the poor prognosis group was significantly lower than that in the favorable prognosis group,while the T2WI signal intensity index,T1WI signal intensity index and plaque enhancement rate in the poor prognosis group were significantly higher than those in the favorable prognosis group(t=-3.378,4.443,4.413,3.890,P<0.05),respectively.ROC curve analysis showed that the area under curve(AUC)values of T2WI signal intensity index,T1WI signal intensity index,lumen area at the narrowest point and plaque enhancement rate in predicting the AIS prognosis were respectively 0.743,0.739,0.706 and 0.748.The Logistic regression analysis showed that infarction diameter>3.0cm,T1WI signal intensity index,T2WI signal intensity index,lumen area at the narrowest point and plaque enhancement rate were respectively independent risk factors that could affect AIS prognosis(OR=3.889,257.151,105.073,4.091,1.121,P<0.05).Conclusion:3.0T HR-MRI has higher efficiency in the assessment for the prognosis of patients with AIS,which can provide guidance for the judgement of prognosis and the formulation of treatment scheme through observes the changes of a series of parameters include T2WI signal strength index,T1WI signal strength index,the lumen area at the narrowest point,plaque enhancement rate.The above parameters are risk factors that affect the prognosis of patients,which often represent the progress of patients'conditions.