BACKGROUND:Intervertebral disc degeneration is an important cause of low back pain.At present,there are many modeling methods for disc degeneration in China and abroad,but there is not a model for low back pain due to disc degeneration. OBJECTIVE:To compare the effect of mechanical puncture combined with tumor necrosis factor α and complete Freund's adjuvant with a conventional disc mechanical puncture alone. METHODS:A total of 18 male adult Sprague-Dawley rats were randomly divided into 3 groups,with 6 animals in each group.No treatment was given in the blank group.Animal models of intervertebral disc degeneration were made in the L4-5 segments of rats in the control using conventional mechanical puncture.In the experimental group,on the basis of mechanical puncture,tumor necrosis factor α+complete Freund's adjuvant was injected into the L4-5 intervertebral discs using a microinjector to establish a model of disc degeneration induced by mechanical puncture combined with inflammatory factors.Four weeks after surgery,the pain threshold of rats was measured by the hot plate method for assessing the perception of heat injury in rats with intervertebral disc degeneration.MRI examination was performed to observe the disc degeneration in each group.ELISA was used to detect the levels of serum tumor necrosis factor α,interleukin 1β,interleukin 6 and prostaglandin E2.Hematoxylin-eosin and Safranin O-fast green staining were used to observe the morphological changes of the disc. RESULTS AND CONCLUSION:In terms of pain,the behavioral pain threshold of the experimental group was continuously decreased,and the levels of serum inflammatory factors were significantly higher compared with the control group.In terms of morphology,the MRI results showed that the L4-5 nucleus pulposus signal completely disappeared in the experimental group.Histopathological results showed that in the control group,the nucleus pulposus was intact,more notochord cells were visible,and some fiber rings were ruptured,while in the experimental group,there are fewer notochord cells and the structure of the nucleus pulposus and fibrous ring is disturbed,with the boundary disappearing.To conclude,mechanical puncture combined with tumor necrosis factor alpha and complete Freund's adjuvant can successfully establish a discogenic low back pain model in rats.This operation is simple and economical to achieve obvious disc degeneration and low back pain,with greatly shortened molding cycle.This model can be used as a reference for studying discogenic low back pain models.

ObjectiveTo investigate the efficacy and safety of cinobufagin tablets combined with thalidomide/dexamethasone （TD） regimen in the treatment of newly diagnosed multiple myeloma （NDMM） with phlegm and stasis obstruction. MethodsThe clinical data of 50 patients with NDMM of phlegm and stasis obstruction who were hospitalized at the Jiangsu Province Hospital of Chinese Medicine from June 1st， 2015 to July 31th， 2019 were retrospectively analyzed， and they were divided into a control group （bortezomib/dexamethasone-containing regimen， 27 cases） and an observation group （cinobufagin tablets combined with TD regimen， 23 cases）. The clinical efficacy and safety were compared between the two groups after two or three courses of treatment. The primary outcomes were clinical remission rate including overall response rate and deep remission rate， one-year and two-year overall survival rate， and adverse effects. The secondary outcomes were the proportion of plasma cells in bone marrow， hemoglobin， β2-microglobulin， lactate dehydrogenase， serum creatinine， blood urea nitrogen， bone pain score， and KPS functional status score （KPS score） before and after treatment. ResultsIn terms of clinical efficacy， there was no statistically significant difference （P＞0.05） in the overall response rate ［the observation group 69.57%（16/23） vs the control group 70.37% （19/27）］ and deep remission rate ［the observation group 56.52% （13/23） vs the control group 55.56% （15/27）］ between groups after the treatment. The one-year overall survival rates of the observation group and the control group were 90.9% and 92.4%， and the two-year overall survival rates were 81.8% and 80.9% respectively， with no statistically significant differences between groups （P＞0.05）. During the treatment， no renal function injury occurred in both groups. The incidence of peripheral nerve injury in the observation group was 8.70%， which was lower than 48.15% in the control group （P＜0.01）. After the treatment， the proportion of myeloma plasma cells， β2-microglobulin， serum creatinine level， and bone pain score decreased， while the hemoglobin level and KPS score increased in both groups （P＜0.05 or P＜0.01）. Compared between groups after treatment， the bone pain score of the observation group was lower than that of the control group， while the KPS score was higher than that of the control group （P＜0.05）. ConclusionThe clinical efficacy of cinobufagin tablets combined with TD in the treatment of NDMM is equivalent to bortezomib/dexamethasone-containing regimen， but the former is more helpful in relieving the pain and improving the quality of life， and has better safety.

Objective To analyze the clinical application value of cinematic rendering(CR)reconstruction technology in acute aortic dissection(AAD),and to compare the imaging quality between CR and volume rendering(VR)reconstruction.Methods Patients with suspected A AD who underwent aortic computed tomography angiography(CTA)were analyzed retrospectively.All images were uploaded to Siemens Syngo.via post-processing workstation for VR and CR three-dimensional reconstruction,respectively.The optimized view angle,staining and transparency were selected and segmented by a radiologist to display the lesion to the full extent.All subjective evaluations of post-processing images were randomly evaluated on Siemens Syngo.via post-processing workstation by two radiologists.The two radiologists reached a consensus after consultation,and the results without consensus were evaluated by another senior radiologist.The 3-point scale was used in the subjective evaluation of post-processing images.The scores of rupture,endometrium,and true and false cavity were recorded.The diagnostic confidence was also recorded.Results A total of 21 ADD patients were enrolled,11 patients(52.3％)were Debakey Ⅲ type.The scores of rupture in CR and VR reconstruction were 2.952 points and 2.619 points,respectively,which had significant difference(P=0.016).For the endometrium of AAD,the score of all 21 patients in the CR reconstruction was 3 points,while only 7 patients(33.3％)in the VR reconstruction had 3 points,which showed significant difference between the both(P＜0.001).For the true and false cavity of AAD,only 1 patient(4.8％)in the VR reconstruction was 3 points,while all 21 patients in the CR reconstruction had 3 points(P＜0.001).The scores of CR reconstruction on the diagnostic confidence were significantly higher than those of VR reconstruction(P＜0.001).Conclusion CR reconstruction can provide photorealistic anatomical post-processing images,and can improve the display and evaluation of AAD.

Objective:To analyze the relationship between CT attenuation value of pulmonary artery thrombi and the efficacy of interventional thrombolysis in patients with acute pulmonary embolism (APE).Methods:This was a single center cross-sectional study. The clinical and imaging data of 89 APE patients who underwent interventional thrombolysis in Affiliated Hospital of Xuzhou Medical University from January 2018 to December 2022, were retrospectively analyzed. All patients underwent CT pulmonary angiography (CTPA) before and after thrombolysis, the CT attenuation value of pulmonary artery thrombi and ratio of CT attenuation value of thrombi to left subscapularis muscle CT value were obtained; and the difference of Qanadli embolism index (ΔQ) before and after thrombolysis was calculated. According to the median ΔQ, patients were classified as good efficacy group (ΔQ>50%) and poor efficacy group (ΔQ≤50%). The clinical characteristics and quantitative parameters of CT were compared between the two groups, and the factors associated with efficacy of thrombolysis were analyzed with univariate and multivariate logistic regression. The correlation between CT attenuation value of pulmonary artery thrombi and ΔQ was analyzed by Spearman correlation analysis.Results:The CT attenuation value of thrombi and ratio of attenuation value of thrombi to left subscapularis muscle CT value showed significant difference between the two groups ( P<0.05). Multivariate analysis showed that compared with CT attenuation value of emboli≤53.47 HU, the value>53.47 HU might be associated with the good efficacy of thrombosysis ( OR=9.175, 95% CI: 0.937-89.846, P=0.057). There was a positive correlation between CT value of pulmonary artery thrombi and ΔQ ( r=0.365, P<0.001). Conclusion:The CT attenuation value of thrombi can predict the efficacy of interventional thrombolysis in APE patients, and patients with higher CT attenuation value would have a better treatment response.

Objective:To investigate the application of transbronchial needle aspiration (TBNA) in the diagnosis of tuberculosis with mediastinal lymphadenopathy in children.Methods:A retrospective study was conducted on clinical data in 8 children of tuberculosis with mediastinal lymphadenopathy treated in the Center for Respiratory Intervention, Children′s Hospital Affiliated to Shandong University from March 2014 to July 2019.TBNA was performed after the mediastinal lymphadenopathy were diagnosed by chest enhanced CT and the final diagnosis was made.The diagnostic experience of TBNA was summarized.Results:Eight children with mediastinal lymphadenopathy included in this present study aged from 7 months to 8 years and 6 months (infants accounted for 75.0%), with a median age of 22.5 months.There were 3 males (37.5%) and 5 females (62.5%). The body mass was 8.5-39.0 kg, and the median body mass was 10.7 kg.The course of disease was 15-90 days, and the median number of days was 18.5 days.The clinical manifestations included cough in 8 cases, fever in 4 cases, wheezing in 1 case and laryngeal ringing in 1 case.Bronchoscopy and TBNA biopsy were performed.Cytology, etiology and pathology were examined after TBNA.A definite diagnosis could be made in 6 children, with a diagnosis rate of 75.0%.Among them, 4 cases were found with acid-fast bacilli in smear but pathological examination was negative; 1 case was pathologically conformed to the characteristics of tuberculosis infection but the smear was negative; the smear and pathology of 1 case were both suggestive of tuberculosis; 2 cases did not present etiological and histological evidence with TBNA.The diagnosis was made according to the positive acid-fast bacilli of alveolar lavage fluid smear.There were no complications during and after operation.Conclusions:TBNA is an important method to diagnose tuberculosis in children, which is effective, safe and has high clinical application value.

Alternative polyadenylation(APA)is a crucial step in post-transcriptional regulation.Previous bioinformatic studies have mainly focused on the recognition of polyadenylation sites(PASs)in a given genomic sequence,which is a binary classification problem.Recently,computa-tional methods for predicting the usage level of alternative PASs in the same gene have been pro-posed.However,all of them cast the problem as a non-quantitative pairwise comparison task and do not take the competition among multiple PASs into account.To address this,here we propose a deep learning architecture,Deep Regulatory Code and Tools for Alternative Polyadenylation(DeeReCT-APA),to quantitatively predict the usage of all alternative PASs of a given gene.To accommodate different genes with potentially different numbers of PASs,DeeReCT-APA treats the problem as a regression task with a variable-length target.Based on a convolutional neural network-long short-term memory(CNN-LSTM)architecture,DeeReCT-APA extracts sequence features with CNN layers,uses bidirectional LSTM to explicitly model the interactions among com-peting PASs,and outputs percentage scores representing the usage levels of all PASs of a gene.In addition to the fact that only our method can quantitatively predict the usage of all the PASs within a gene,we show that our method consistently outperforms other existing methods on three different tasks for which they are trained:pairwise comparison task,highest usage prediction task,and rank-ing task.Finally,we demonstrate that our method can be used to predict the effect of genetic variations on APA patterns and sheds light on future mechanistic understanding in APA regulation.

The accurate annotation of transcription start sites(TSSs)and their usage are critical for the mechanistic understanding of gene regulation in different biological contexts.To fulfill this,specific high-throughput experimental technologies have been developed to capture TSSs in a genome-wide manner,and various computational tools have also been developed for in silico pre-diction of TSSs solely based on genomic sequences.Most of these computational tools cast the problem as a binary classification task on a balanced dataset,thus resulting in drastic false positive predictions when applied on the genome scale.Here,we present DeeReCT-TSS,a deep learning-based method that is capable of identifying TSSs across the whole genome based on both DNA sequence and conventional RNA sequencing data.We show that by effectively incorporating these two sources of information,DeeReCT-TSS significantly outperforms other solely sequence-based methods on the precise annotation of TSSs used in different cell types.Furthermore,we develop a meta-learning-based extension for simultaneous TSS annotations on 10 cell types,which enables the identification of cell type-specific TSSs.Finally,we demonstrate the high precision of DeeReCT-TSS on two independent datasets by correlating our predicted TSSs with experimentally defined TSS chromatin states.The source code for DeeReCT-TSS is available at https://github.-com/JoshuaChou2018/DeeReCT-TSS_release and https://ngdc.cncb.ac.cn/biocode/tools/BT007316.

Objective:To study the diagnostic value of non-enhanced lesions on enhanced CT in lung consolidation for necrotizing pneumonia in children.Methods:A total of 101 cases of necrotizing pneumonia with air sacs on CT scan who were hospitalized in the Department of Respiratory Intervention, Qilu Children′s Hospital of Shandong University from August 2016 to September 2018 were enrolled in this study(group with air lucency). Besides, another 75 cases of lobar pneumonia with non-enhanced lesions in lung consolidation but without air sacs on enhanced CT were also included from the same hospital over the same period(group without air lucency). Clinical data of these patients were retrospectively collected and statistically analyzed.Results:The white blood cell count was (12.5±5.5)×10 9/L in group with air sacs and (10.8±4.1)×10 9/L in group without air sacs, and the difference was statistically significant( t=-2.161, P=0.032). There was no statistical difference between the group with and without air sacs in age, gender distribution, the course prior to admission, duration of fever after admission, length of hospital stay, medical expense, the neutrophils percentage in peripheral blood, C-reactive protein, the erythrocyte sedimentation rate, serum procalcitonin, serum D-Dimer, serum lactate dehydrogenase, serum albumin, bronchoscopy times, the bronchial mucosal erosion ratio, the mucus plug score, the lavage purulent lavage ratio, and the ratio of luminal stricture or atresia in late bronchoscopy(all P>0.05). Conclusions:The clinical course of patients with non-enhanced lesions in lung consolidation but without air sacs is almost identical to that of patients with air sacs on CT scan.The presence of non-enhanced lesions in lung consolidation can be used as diagnostic basis of necrotizing pneumonia in children.

Objective:To study the early predictors of Mycoplasma pneumoniae necrotizing pneumonia in children.Methods:Clinical data of 291 children with lobar pneumonia caused by Mycoplasma pneumoniae who were hospitalized in Department of Respiratory Intervention, Qilu Children′s Hospital of Shandong University from August 2016 to September 2018, were retrospectively analyzed.The patients were divided into necrotizing pneumonia group (154 cases) and non-necrotizing pneumonia group (137 cases). After comparing clinical characteristics, laboratory tests, and bronchoscopy findings, multivariate logistic regression analysis was carried out on the indicators with statistical significance to obtain the independent predictive indicators of Mycoplasma pneumoniae necrotizing pneumonia, and then the cutoff value with the maximum diagnostic value of each indicator was found through receiver operating characteristic (ROC) curve analysis.Results:There were no significant differences in gender and age distribution, duration before admission, and platelet count between the 2 groups(all P>0.05). Necrotizing pneumonia group manifested with 11.0(8.3-14.4)×10 9/L of white blood cell count, 0.740±0.115 of neutrophil, 44.2(21.2-72.0) mg/L of C-reactive protein(CRP), 55(35-80) mm/1 h of erythrocyte sedimentation rate, 0.19(0.08-0.60) ng/L of procalcitonin, 2.63(1.62-3.79) mg/L of plasma D-dimer, 456(340-665) U/L of serum lactate dehydrogenase, (35.6±4.3) g/L of serum albumin, 121 cases(78.6%)of bronchoscopic mucosal erosion, 75 cases(48.7%)of purulent lavage, 119 cases(77.3%)of massive secretions embolism; non-necrotizing pneumonia group manifested with 8.7(6.9-11.6)×10 9/L of white blood cell count, 0.660±0.127 of neutrophil percentage, 15.9(7.5-34.3) mg/L of CRP, 45(30-60) mm/1 h of erythrocyte sedimentation rate, 0.10(0.06-0.20) ng/L of procalcitonin, 0.69(0.46-1.24) mg/L of plasma D-dimer, 314(250-419) U/L of serum lactate dehydrogenase, (38.9±3.7) g/L of serum albumin, 53 cases(38.7%)of bronchoscopic mucosal erosion, 20 cases(14.6%)of purulent lavage, and 76 cases(55.5%)of massive secretions embolism.All the above indicators had statistical differences between the 2 groups.Erythrocyte sedimentation rate, serum lactate dehydrogenase, D-dimer, and bronchoscopic mucosal erosion were independent predictors of Mycoplasma necrotizing pneumonia.The area under the ROC curve were 0.643, 0.749, 0.858 and 0.699, respectively, with the cut off point of 53 mm/1 h, 335 U/L, and 1.36 mg/L, respectively. Conclusions:Erythrocyte sedimentation rate≥53 mm/1 h, serum lactate dehydrogenase≥335 U/L, D-dimer≥1.36 mg/L, and bronchoscopic mucosal erosion are early independent predictors of Mycoplasma necrotizing pneumonia in children, among which D-dimer has the highest value.

Objective:To investigate the diagnostic value of rapid on-site evaluation (ROSE) technique in the mucosal biopsy under respiratory endoscopy in children with active tuberculosis.Methods:Clinical data of 40 patients with active tuberculosis diagnosed in Department of Respiratory Intervention, Qilu Children′s Hospital, Shandong University from June 2017 to January 2020 were retrospectively analyzed.Results:(1) There were 33 cases of tracheobronchial tuberculosis and 7 cases of tuberculous pleurisy in the 40 cases, among them 9 cases were difficult to diagnose.(2)Among 33 cases of tracheobronchial tuberculosis, 24 cases (72.7%) of caseous necrosis breaking into the lumen, and 9 cases (27.3%) of mucosal swelling and external pressure.Cytological ROSE (C-ROSE) showed granuloma, epithelioid cells and lymphocytic infiltration with all bronchial mucosal biopsies.Different positives results of microbiological ROSE (M-ROSE) in different biopsy parts: positive results were found 6 times at caseous necrosis (13.6%, 6/44 times), 4 times at granulation hyperplasia (12.5%, 4/32 times), 2 times at hyperemia and edema (22.2%, 2/18 times), 0 time at yellow-white necrosis, and 54 times at the junction between lesions and normal mucosa (81.8%, 54/66 times). The mucosal pathology showed granuloma, exudation and necrosis, including 22 cases with tuberculous granuloma, 5 cases with characteristic tuberculous nodules, and 11 cases with positive acid-fast staining.(3)Seven cases of tuberculous pleurisy, serious pleural adhesion, pleural hyperemia and edema were observed under thoracoscopy.After clearing the adhesive tape, scattered caseous miliary nodules were found in pleura in 4 cases with a difficult clinical diagnosis.The C-ROSE of smear on thoracoscopic biopsy were characterized by necrotic and histopathic cell, with multinucleated giant cells, but granuloma was rare.M-ROSE in different parts: 8 times positive for millet nodules (80.0%), 0 time positive for adhesion band, 2 times positive for congestion oedema (14.3%); biopsy pathology showed granuloma and necrosis, with 3 cases characteristic tuberculosis nodules and 2 cases positive for anti-acid staining.(4)Pathogenic microorganisms were detected in 19 children using next generation sequencing (NGS) and Mycobacterium tuberculosis/Rifampicin resistance real-time nucleic acid amplification detection technology (Xpert MTB/RIF), including 7 positive for NGS (36.8%), 8 positive (42.1%) and 5 positive for both NGS and Xpert MTB/RIF (26.3%).Conclusions:Respiratory endoscopy combined with ROSE technique has important clinical significance in early diagnosis of active tuberculosis in children, and it is worth of promotion and applying.